acid-phosphatase and Inflammation

Adenosine receptor agonists have potent antinociceptive effects in diverse preclinical models of chronic pain. By contrast, the efficacy of adenosine and adenosine receptor agonists in treating pain in humans is unclear. Two ectonucleotidases that generate adenosine in nociceptive neurons were recently identified. When injected spinally, these enzymes have long-lasting adenosine A(1) receptor-dependent antinociceptive effects in inflammatory and neuropathic pain models. Furthermore, recent findings indicate that spinal adenosine A(2A) receptor activation can enduringly inhibit neuropathic pain symptoms. Collectively, these studies suggest the possibility of treating chronic pain in humans by targeting specific adenosine receptor subtypes in anatomically defined regions with agonists or with ectonucleotidases that generate adenosine.

Topics: 5'-Nucleotidase; Acid Phosphatase; Acupuncture Therapy; Adenosine; Adenosine Monophosphate; Analgesics; Animals; Humans; Hyperalgesia; Inflammation; Neuralgia; Nociceptors; Protein Tyrosine Phosphatases; Purinergic P1 Receptor Agonists; Receptors, Purinergic P1; Recombinant Proteins

Topics: Acid Phosphatase; Animals; Cathepsins; Chediak-Higashi Syndrome; Fabry Disease; Inflammation; Keratins; Langerhans Cells; Light; Lysosomes; Melanophores; Microscopy, Electron; Peptide Hydrolases; Phagocytosis; Pigmentation; Protease Inhibitors; Sebaceous Glands; Skin; Skin Diseases; Skin Neoplasms; Vitamin A

Topics: Acid Phosphatase; Antigen-Antibody Reactions; Antigens, Bacterial; Dental Plaque; Gingiva; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunoglobulins; Inflammation; Lymphocytes; Periodontal Diseases; Streptococcus mutans; Sucrose

Topics: Acid Phosphatase; Alkaline Phosphatase; Endothelium; Eosinophils; Esterases; Fibroblasts; Histiocytes; Histocytochemistry; Humans; Inclusion Bodies; Inflammation; Leucyl Aminopeptidase; Mast Cells; Monocytes; Neutrophils; Peroxidases; Plasma Cells; Reticulocytes; Skin; Skin Physiological Phenomena

Topics: Acid Phosphatase; Aged; Arthritis, Rheumatoid; Body Temperature; Calcinosis; Female; Humans; Inflammation; Joint Diseases; Kinins; Knee Joint; Lysosomes; Male; Middle Aged; Proteins; Psoriasis; Synovial Fluid

OBJECTIVE To explore the changes of bone gla protein (BGP) and tartrate resistant acid phosphatase (TRACP) in patients with stage 3 -4 chronic kidney disease (CKD) before and after treatment, to study their correlation with interleukin-17 (IL-17) and regulatory T cells (Treg), and the effects of Yishen Jiangzhuo Granule (YJG) on the bone metabolism.. Fifty-three patients with stage 3-4 CKD were randomly assigned to the treatment group and the control group using random digit table. The following parameters in blood were detected: Treg (CD4+ CD25+ CD127lo) using tri-chrism fluorescent labeling by flow cytometry; levels of TRACP, BGP, and IL-17 by double antibody sandwich ELISA. The hemoglobin (HGB) content was detected using Beckman-Coulter heme/analysis. The urinary contents of creatinine (UCr) were determined using reversed HPLC. The blood contents of calcium (Ca), phosphate (P), blood urea nitrogen (BUN), serum creatinine (SCr), and plasma albumin (ALB) were determined using automatic biochemical analyzer. Then the calcium-phosphate (Ca x P) product was calculated on the basis of blood contents of Ca and P. The clearance rate of endogenous creatinine (CCr) was calculated on the basis of blood BUN and SCr contents.. (1) There was no obvious change in CD4+ CD25+ CD127lo in the two groups before and after treatment (P > 0.05). Compared with before treatment in the same group, there were statistical difference in the levels of CD4+ and TRACP in the two groups, as well as the IL-17 level in the control group (P < 0.01, P < 0.05). But compared with the healthy group, statistical difference was shown in each index (except CD4+) (P < 0.01). Compared with the control group after treatment, there was no statistical difference in each index of the treatment group after treatment (P > 0.05). Compared with before treatment in the same group, the levels of Hb, ALB, and CCr increased (P < 0.05, P < 0.01), and the SCr level decreased in the two groups after treatment (P < 0.05). Compared with the control group after treatment, the SCr level decreased and the CCr level increased more obviously in the treatment group (P < 0.05). There was no correlation among the levels of IL-17, TRACP, BGP, and Treg between before and after treatment in the two groups.. YJG could improve the kidney function and delay the progression of micro-inflammation of stage 3 -4 CKD patients. It could not improve the level of CD4+ CD25+ CD127lo. It also showed no effects on bone metabolism. The CD4+ T cells were differentiated to Th17 cells in stage 3-4 CKD patients. Their immunity was in a state of anergy but continually activated. The inflammatory factors in patients with stage 3-4 CKD play important roles in inducing the activation of osteoclasts.

Topics: Acid Phosphatase; Adult; Aged, 80 and over; Bone and Bones; Drugs, Chinese Herbal; Female; Humans; Inflammation; Interleukin-17; Isoenzymes; Male; Middle Aged; Osteocalcin; Renal Insufficiency, Chronic; T-Lymphocytes, Regulatory; Tartrate-Resistant Acid Phosphatase

Secondary hyperparathyroidism (SHP) is characterized by high bone turnover and elevated serum bone remodeling markers. Elevation of serum interleukin-6 (IL-6) levels is also characteristic of end-stage renal disease. This study investigates the effects of intravenous calcitriol on serum bone resorptive markers, namely, type 5b tartrate-resistant acid phosphatase (TRACP5b) and IL-6 in patients with SHP.. Intravenous calcitriol therapy was given for 16 weeks to 24 patients on maintenance hemodialysis with plasma intact parathyroid hormone (iPTH) levels >300 pg/ml. Blood was drawn at baseline and every 4 weeks for 16 weeks for determination of the levels of biochemical parameters, iPTH, IL-6 and bone remodeling markers, including bone-specific alkaline phosphatase (bAP) and TRACP5b.. Only 21 patients responded to the calcitriol therapy, with significant decrements in serum iPTH after 4 weeks of therapy and thereafter. After 16 weeks of calcitriol therapy, 21 patients had significant decrements in serum iPTH (707.9 +/- 317.8 vs. 205.0 +/- 63.1 pg/ml, p < 0.01). Prior to treatment, a significant correlation was found between increased levels of serum iPTH and IL-6 levels (r = 0.45, p < 0.05). After treatment, there was also a significant and parallel lowering of levels of serum iPTH, IL-6 (8.52 +/- 3.59 vs. 7.24 +/- 2.81 pg/ml, p < 0.01), bAP (54.68 +/- 36.17 vs. 24.55 +/- 13.84 U/l, p < 0.01) and TRACP5b (3.41 +/- 1.89 vs. 1.80 +/- 0.55 U/l, p < 0.01). Our results additionally showed significant positive correlationsbetween baseline levels of serum IL-6 and those of iPTH, bAP and TRACP5b. After 16 weeks of calcitriol treatment, the correlation between IL-6 and iPTH levels lost significance but levels of serum IL-6, bAP and TRACP5b remained significantly correlated.. Elevated levels of serum IL-6 and bone remodeling markers, namely, bAP and TRACP5b which are common features of SHP, are effectively suppressed by calcitriol therapy. This indicates that hyperparathyroidism not only accelerates bone remodeling but may also aggravate inflammation in patients on maintenance hemodialysis.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone Density Conservation Agents; Bone Resorption; Calcitriol; Female; Humans; Hyperparathyroidism, Secondary; Inflammation; Interleukin-6; Isoenzymes; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Time Factors

Focal bone microcracks with osteoclast recruitment and bone lysis, may reduce fracture resistance in racehorses. As current imaging does not detect all horses at risk for fracture, the discovery of novel serum biomarkers of bone resorption or osteoclast activity could potentially address this unmet clinical need. The biology of equine osteoclasts on their natural substrate, equine bone, has never been studied in vitro and may permit identification of specific biomarkers of their activity.. (1) Establish osteoclast cultures on equine bone, (2) Measure biomarkers (tartrate resistant acid phosphatase isoform 5b [TRACP-5b] and C-terminal telopeptide of type I collagen [CTX-I]) in vitro and (3) Study the effects of inflammation.. In vitro experiments.. Haematopoietic stem cells, from five equine sternal bone marrow aspirates, were differentiated into osteoclasts and cultured either alone or on equine bone slices, with or without a pro-inflammatory stimulus (IL-1β or LPS). CTX-I and TRACP-5b were immunoassayed in the media. Osteoclast numbers and bone resorption area were assessed.. TRACP-5b increased over time in osteoclast cultures without bone (p < 0.0001) and correlated with osteoclast number (r = 0.63, p < 0.001). CTX-I and TRACP-5b increased with time for cultures with bone (p = 0.002; p = 0.02 respectively), correlated with each other (r = 0.64, p < 0.002) and correlated with bone resorption (r = 0.85, p < 0.001; r = 0.82, p < 0.001 respectively). Inflammation had no measurable effects.. Specimen numbers limited.. Equine osteoclasts were successfully cultured on equine bone slices and their bone resorption quantified. TRACP-5b was shown to be a biomarker of equine osteoclast number and bone resorption for the first time; CTX-I was also confirmed to be a biomarker of equine bone resorption in vitro. This robust equine specific in vitro assay will help the study of osteoclast biology.. Fokale Mikrofrakturen im Knochen mit Osteoklasten Rekrutierung und Knochen Lyse können die Frakturresistenz bei Rennpferden verringern. Da die derzeitige Bildgebung nicht alle Pferde mit Frakturrisiko erfasst, könnte die Entdeckung neuer Serum-Biomarker für die Knochenresorption oder Osteoklasten Aktivität diesen ungedeckten klinischen Bedarf möglicherweise decken. Die Biologie der Pferde Osteoklasten auf ihrem natürlichen Substrat, dem Pferdeknochen, wurde noch nicht in vitro untersucht und könnte die Identifizierung spezifischer Biomarker für ihre Aktivität ermöglichen. ZIELE: (1) Anlegen von Osteoklastenkulturen an Pferdeknochen, (2) Messung von Biomarkern (tartrate resistant acid phosphatase isoform 5b [TRACP-5b] und C-terminal telopeptide of type I collagen [CTX-I]) in vitro und (3) Untersuchung der Auswirkungen von Entzündungen.. In vitro experimentelle Studie.. Hämatopoetische Stammzellen aus fünf sternalen Knochenmark Aspiraten von Pferden wurden in Osteoklasten differenziert und entweder alleine oder auf Knochenscheiben von Pferden kultiviert, mit oder ohne proinflammatorischen Stimulus (IL 1β oder LPS). CTX-I und TRACP-5b wurden in den Medien immunoassayiert. Die Anzahl der Osteoklasten und die Fläche der Knochenresorption wurden bestimmt.. TRACP 5b nahm mit der Zeit ohne Knochen zu (p < 0.0001) und korrelierte mit der Osteoklasten Anzahl (r = 0.63, p < 0.001). CTX-I und TRACP-5b nahmen bei Kulturen mit Knochen mit der Zeit zu (p = 0.0018 bzw. p = 0.02), korrelierten miteinander (r = 0.64, p < 0.002) und korrelierten mit der Knochenresorption (r = 0.85, p < 0.001 bzw. r = 0.82, p < 0.001). Entzündungen hatten keine messbaren Auswirkungen. WICHTIGSTE EINSCHRÄNKUNGEN: Limitierte Probenanzahl.. Osteoklasten von Pferden wurden erfolgreich auf Knochenscheiben von Pferden kultiviert und ihre Knochenresorption quantifiziert. TRACP-5b erwies sich zum ersten Mal als Biomarker für die Anzahl der Osteoklasten und die Knochenresorption bei Pferden; CTX-I wurde ebenfalls als Biomarker für die Knochenresorption bei Pferden in vitro bestätigt. Dieser robuste pferdespezifische in-vitro-Assay wird die Untersuchung der Osteoklasten Biologie unterstützen.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone Resorption; Fractures, Bone; Horse Diseases; Horses; Inflammation; Isoenzymes; Osteoclasts; Tartrate-Resistant Acid Phosphatase

In recent years, several studies have demonstrated that the RNASET2 gene is involved in the control of tumorigenicity in ovarian cancer cells. Furthermore, a role in establishing a functional cross-talk between cancer cells and the surrounding tumor microenvironment has been unveiled for this gene, based on its ability to act as an inducer of the innate immune response. Although several studies have reported on the molecular features of RNASET2, the details on the mechanisms by which this evolutionarily conserved ribonuclease regulates the immune system are still poorly defined. In the effort to clarify this aspect, we report here the effect of recombinant human RNASET2 injection and its role in regulating the innate immune response after bacterial challenge in an invertebrate model, the medicinal leech. We found that recombinant RNASET2 injection induces fibroplasias, connective tissue remodeling and the recruitment of numerous infiltrating cells expressing the specific macrophage markers CD68 and HmAIF1. The RNASET2-mediated chemotactic activity for macrophages has been further confirmed by using a consolidated experimental approach based on injection of the Matrigel biomatrice (MG) supplemented with recombinant RNASET2 in the leech body wall. One week after injection, a large number of CD68

Topics: Acid Phosphatase; Animals; Cell Proliferation; Collagen; Connective Tissue; Cryoultramicrotomy; Drug Combinations; Enzyme Assays; Fluorescent Antibody Technique; Hirudo medicinalis; Humans; Inflammation; Laminin; Lipopolysaccharides; Macrophages; Proteoglycans; Recombinant Proteins; Ribonucleases; Tumor Suppressor Proteins

We determined effects of bariatric weight loss surgery on serum tartrate-resistant acid phosphatase 5a (TRACP 5a), inflammatory cytokines and glucose homeostasis in severely obese Chinese adults.. Severely obese adults undergoing bariatric surgery were recruited. Anthropometry, insulin resistance (IR), inflammatory markers and serum TRACP 5a were measured at baseline and 3, 6 and 12months postoperatively.. Data of 93 patients, including 69 non-diabetic (non-DM group) and 24 diabetic (DM group), were analyzed. Anthropometry decreased significantly at 3months postoperatively in both groups; low-density lipoprotein cholesterol decreased obviously at 3, 6 and 12months in non-DM group, while improving significantly at 6 and 12months in DM group. Homeostasis model assessment for IR (HOMA-IR) improved significantly at 3, 6 and 12months in non-DM group and 12months in DM group. In DM group, C-reactive protein (CRP) decreased significantly at 3months postoperatively and inflammatory markers interleukin-6 (IL-6) and TRACP 5a improved at 6months postoperatively; in non-DM group, serum TRACP 5a decreased obviously at 12months postoperatively without significant changes in CRP and IL-6.. Weight reduction by bariatric surgery decreases anthropometry, IR, lipids and inflammatory markers in severely obese Chinese adults.

Topics: Acid Phosphatase; Adult; Asian People; Bariatric Surgery; Blood Glucose; C-Reactive Protein; Case-Control Studies; Cytokines; Female; Humans; Inflammation; Insulin Resistance; Isoenzymes; Lipids; Male; Obesity; Tartrate-Resistant Acid Phosphatase; Weight Loss

Aseptic loosening associated with wear particle-induced inflammation is a major cause of joint implant failure. Recent studies have demonstrated the therapeutic effects of p38 mitogen-activated protein kinase (MAPK)-based therapies on chronic inflammatory diseases. The purpose of this study was to investigate whether SB203580, a p38 MAPK inhibitor, inhibits wear debris-induced inflammatory osteolysis in mice through downregulation of receptor activator of nuclear factor kβ (RANK)/RANK ligand (RANKL). We used a murine osteolysis model to study the effect of SB203580 on RANKL/RANK signaling and titanium particle-induced osteolysis in vivo. Pouch membranes with intact bone implants were analyzed using histological analysis and transmission electron microscopy, and the levels of RANK and RANKL protein and mRNA were evaluated by immunohistological staining and real-time reverse transcriptase-polymerase chain reaction. SB203580 had less of an effect on RANK and RANKL expression under wear debris-induced conditions. The number of TRAP-positive cells was remarkably reduced in Ti-particle-induced pouch tissues. These effects were confirmed through the transmission electron microscopy results. These results suggest that p38 MAPK-based therapies are beneficial in preventing aseptic loosening associated with total joint replacement by modulating RANK-RANKL signaling.

Topics: Acid Phosphatase; Animals; Bone and Bones; Colonic Pouches; Disease Models, Animal; Down-Regulation; Female; Immunohistochemistry; Inflammation; Isoenzymes; Mice, Inbred BALB C; Osteolysis; p38 Mitogen-Activated Protein Kinases; Prostheses and Implants; Protective Agents; Protein Kinase Inhibitors; RANK Ligand; Real-Time Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; Tartrate-Resistant Acid Phosphatase; Titanium

Intestinal mucosal immune components and mRNA levels of inflammatory cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules in young grass carp (Ctenopharyngodon idellus) under dietary manganese (Mn) deficiency or excess were investigated. Fish were fed the diets containing graded levels of Mn [3.65-27.86 mg Mn kg(-1) diet] for 8 weeks. The results demonstrated that Mn deficiency significantly decreased the lysozyme and acid phosphatase (ACP) activities, up-regulated tumour necrosis factor α (TNF-α), interleukin 8 and the signalling factor nuclear factor-κB p65, and down-regulated interleukin 10 (IL-10), transforming growth factor β1, inhibitor of signalling factors κB-α and target of rapamycin mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI). However, Mn deficiency did not change the C3 content in the PI, whereas it decreased the C3 contents in the MI and DI. Additionally, Mn depletion also resulted in significantly low mRNA levels for tight junction proteins (claudin-b, claudin-c, claudin-15, occludin and zonula occludens-1), antioxidant enzymes (MnSOD, GPx and CAT) and NF-E2-related factor-2 in the intestines of fish. Excessive Mn exhibited toxic effects similar to Mn deficiency, where optimal Mn contents reversed those indicators. In conclusion, Mn deficiency or excess causes the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier relating to NF-κB, TOR and Nrf2 signalling in grass carp. Furthermore, quadratic regression analysis at 95% maximum response of lysozyme and acid phosphatase activities in the distal intestine of young grass carp revealed the optimum dietary Mn levels to be 8.90 and 8.99 mg kg(-1) diet, respectively.

Topics: Acid Phosphatase; Animals; Carps; Complement C3; Cytokines; Diet; Fish Proteins; Inflammation; Intestinal Mucosa; Manganese; Muramidase; NF-E2-Related Factor 2; NF-kappa B; RNA, Messenger; Signal Transduction; Tight Junction Proteins; TOR Serine-Threonine Kinases

Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia, characterized by metaphyseal lesions, neurological impairment and immune dysregulation associated with lupus-like features. SPENCD is caused by biallelic mutations in the ACP5 gene encoding tartrate-resistant phosphatase. We report on a child, who presented with spasticity, multisystem inflammation, autoimmunity and immunodeficiency with minimal metaphyseal changes due to compound heterozygosity for two novel ACP5 mutations. These findings extend the phenotypic spectrum of SPENCD and indicate that ACP5 mutations can cause severe immune dysregulation and neurological impairment even in the absence of metaphyseal dysplasia.

Topics: Acid Phosphatase; Autoimmune Diseases; Autoimmunity; Bone Diseases; Child; Female; Humans; Immunologic Deficiency Syndromes; Inflammation; Isoenzymes; Magnetic Resonance Imaging; Muscle Spasticity; Mutation; Osteochondrodysplasias; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed

To investigate the effect of Embelin, an inhibitor of X-Linked Inhibitor of Apoptosis Protein (XIAP), on inflammation and bone erosion in a collagen antibody induced arthritis (CAIA) in mice.. Four groups of mice (n = 6 per group) were allocated: CAIA untreated mice, CAIA treated with Prednisolone (10 mg/kg/day), CAIA treated with low dose Embelin (30 mg/kg/day), and CAIA treated with high dose Embelin (50 mg/kg/day). Joint inflammation was evaluated using clinical paw score and histological assessments. Bone erosion was assessed using micro-CT, tartrate resistant acid phosphatase (TRAP) staining, and serum carboxy-terminal collagen crosslinks (CTX-1) ELISA. Immunohistochemistry was used to detect XIAP protein. TUNEL was performed to identify apoptotic cells.. Low dose, but not high dose Embelin, suppressed inflammation as reflected by lower paw scores (P < 0.05) and lower histological scores for inflammation. Low dose Embelin reduced serum CTX-1 (P < 0.05) and demonstrated lower histological score and TRAP counting, and slightly higher bone volume as compared to CAIA untreated mice. XIAP expression was not reduced but TUNEL positive cells were more abundant in Embelin treated CAIA mice.. Low dose Embelin suppressed inflammation and serum CTX-1 in CAIA mice, indicating a potential use for Embelin to treat pathological bone loss.

Topics: Acid Phosphatase; Animals; Arthritis, Experimental; Benzoquinones; Bone Resorption; Inflammation; Isoenzymes; Mice; Tartrate-Resistant Acid Phosphatase; X-Linked Inhibitor of Apoptosis Protein

We aimed to assess osteoclastogenic potential of peripheral blood mononuclear cells (PBMC) and synovial fluid-derived mononuclear cells (SFMC) in different forms of arthritis and to correlate it with inflammatory mediators within intra-articular and circulatory compartments.. Paired PBMC and SFMC samples of patients with rheumatoid arthritis (RA; n = 10) and psoriatic arthritis (PsA; n = 10), and PBMC of healthy controls were cultured to assess osteoclastogenic potential by the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) and expression of OC-related genes (receptor activator of nuclear factor-κΒ (RANK), cFMS, and TRAP). Osteoclastogenesis was correlated with the arthritis-related inflammatory indicators in serum and synovial fluid (SF).. Number of OCs differentiated from PBMC was significantly higher in RA and PsA compared with control, with RA having more OCs compared with PsA. There was no difference in SFMC OC number between arthritic patients, but RANK expression in OCs differentiated from SFMC was higher in PsA compared with RA. SF of PsA patients more potently induced OC differentiation from control CD3(-)CD19(-)CD56(-)CD11b(+)CD115(+) PBMC compared with RA, paralleled with higher RANK-ligand expression in PsA SFMC. Positive correlations of OC number with erythrocyte sedimentation rate, serum level of CCL2, and PBMC gene expression of interleukin-18 and Fas-ligand were observed.. Osteoclastogenic potential is systemically enhanced in patients with RA, paralleled by disordered systemic and local expression of proinflammatory mediators, whereas PsA involves specific deregulation in RANKL/RANK axis. Our study reveals arthritis-specific mediators associated with the form of arthritis, indicating clinical relevance for diagnosis and treatment.

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Psoriatic; Arthritis, Rheumatoid; Case-Control Studies; Cell Count; Cell Differentiation; Cells, Cultured; Female; Humans; Inflammation; Isoenzymes; Leukocytes, Mononuclear; Male; Middle Aged; Osteoclasts; Predictive Value of Tests; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptor, Macrophage Colony-Stimulating Factor; Sensitivity and Specificity; Severity of Illness Index; Synovial Fluid; Tartrate-Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase (TRACP) 5a is expressed strongly in inflammatory macrophages (MΦ). Serum TRACP5a is elevated in rheumatoid arthritis patients with extra-articular manifestations of rheumatoid nodules, in a percentage of patients with end-stage chronic kidney disease, and may be a risk marker for acute myocardial infarction. This proof-of-concept study was undertaken in patients with sarcoidosis to further substantiate our hypothesis that TRACP5a protein is a biomarker for macrophages in other chronic inflammatory diseases.. Immunohistochemical staining for TRACP5a and CD68 was performed in tissues of 19 patients with sarcoidosis. We also measured circulating TRACP5a protein and other inflammation biomarkers including interkeukin-6, angiotensin-converting enzyme, and C-reactive protein in 13 patients. Twenty healthy age-matched nonsmoking individuals were used as the reference group.. All sarcoidosis tissues showed strong staining for TRACP5a and CD68 in the non-caseating granulomatous lesions and localized specifically to MΦ, multinucleate giant cells, and epithelioid MΦ. Serum TRACP5a protein was elevated significantly in active sarcoidosis patients compared with the control group, and levels fluctuated with disease activity in one patient studied longitudinally.. TRACP5a protein is expressed abundantly in the granulomatous tissues and may be elevated in a significant proportion of sarcoidosis patients. These findings further support our hypothesis that serum TRACP5a is derived from systemic inflammatory MΦ and thereby may be a biomarker of inflammation for sarcoidosis and also reflect its disease activity.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Chronic Disease; Female; Humans; Inflammation; Interleukin-6; Isoenzymes; Macrophages; Male; Middle Aged; Sarcoidosis; Tartrate-Resistant Acid Phosphatase

Wear-particle-induced osteolysis is considered to be the main reason for revision after arthroplasty. Although the exact mechanism remains unclear, inflammatory osteoclastogenesis plays an important role in this process. Strontium ranelate (SR) was found to have a therapeutic effect on osteoporosis in postmenopausal women. Based on prior studies, the present authors hypothesized that SR prevents wear-particle-induced osteolysis through restraining inflammatory osteoclastogenesis. The present study used 80 male C57BL/J6 mice to test this hypothesis in a murine osteolysis model. All experimental animals were randomly divided into four groups: a control group; a SR group; a titanium group; and a titanium+SR group. Once titanium particles had been implanted in mice, the mice were administered SR (900 mg kg(-1) day(-1)) by gavage for 14 days. After 14 days, the calvaria were collected for micro-computed tomography (μCT), histological and molecular analysis. The results of μCT and histomorphometric analysis demonstrated that SR markedly inhibited bone resorption and the generation of tartrate-resistant acid-phosphatase-positive cells in vivo, compared with titanium-stimulated calvaria. Reverse transcription polymerase chain reaction and ELISAs showed that SR stimulated the mRNA and protein expression of osteoprotegerin, and inhibited gene and protein expression of receptor activators of nuclear factor-kappa B ligand in titanium-particle-charged calvaria. In addition, SR obviously reduced the secretion of tumor necrosis factor-α and interleukin-1β in the calvaria of the titanium group. It was concluded that SR inhibits titanium-induced osteolysis by restraining inflammatory osteoclastogenesis, and that it could be developed as a new drug to prevent and treat aseptic loosening.

Topics: Acid Phosphatase; Animals; Inflammation; Interleukin-1beta; Isoenzymes; Male; Mice, Inbred C57BL; Osteoclasts; Osteogenesis; Osteolysis; Osteoprotegerin; RANK Ligand; RNA, Messenger; Skull; Staining and Labeling; Tartrate-Resistant Acid Phosphatase; Thiophenes; Titanium; Tumor Necrosis Factor-alpha; X-Ray Microtomography

This study evaluates the influence of platelet-rich plasma derived from bone marrow aspirate (PRP-BMA) on the healing of periodontal fenestration defects in rats.. Periodontal fenestration defects were surgically created in the mandibles of 40 rats. The animals were randomly divided into two groups, control and PRP-BMA, in which defects were filled with blood clot or PRP-bma, respectively. Animals were euthanized at either 10 or 30 days post-surgery. Histologic, histometric, and immunohistochemical analyses were performed. Percentage of new bone area (NBA), area of bone trabeculae (ABT), new cementum (NC), and extension of remaining defect were histometrically evaluated. Proliferating cell nuclear antigen (PCNA), bone sialoprotein (BSP), osteocalcin (OCN), and tartrate-resistant acid phosphatase (TRAP) immunohistochemical staining were performed. Immunolabeled cells were quantified. Data were statistically analyzed (analysis of variance; Tukey, P <0.05).. At 10 days, control and PRP-BMA groups presented similar amounts of NBA and ABT; NC formation was not observed. At 30 days, control and PRP-BMA groups presented similar amounts of NBA and ABT; the PRP-BMA group showed NC formation with collagen fibers inserted obliquely or perpendicularly to the root surface. NC formation was not observed in any control group specimen. PRP- BMA presented higher numbers of PCNA-positive and BSP-positive cells than control at 10 and 30 days post-surgery. No significant differences in the number of either OCN-positive or TRAP-positive cells were observed between groups at 10 or 30 days.. PRP-BMA promoted NC formation with a functional periodontal ligament when applied at experimental periodontal fenestration defects.

Topics: Acid Phosphatase; Alveolar Bone Loss; Animals; Blood Coagulation; Bone Marrow Cells; Bone Regeneration; Cementogenesis; Collagen; Connective Tissue; Dental Cementum; Inflammation; Integrin-Binding Sialoprotein; Isoenzymes; Male; Mandibular Diseases; Necrosis; Osteocalcin; Osteogenesis; Periodontal Ligament; Platelet Count; Platelet-Rich Plasma; Proliferating Cell Nuclear Antigen; Random Allocation; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Time Factors

This study was conducted to evaluate the effect of p-Coumaric acid, a common dietary phenol, on monosodium urate crystal-induced inflammation in rats-an experimental model for acute gouty arthritis.. Paw edema, levels/activities of lysosomal enzymes, lipid peroxidation, enzymic antioxidants and a histopathological examination of ankle joints were evaluated in control and monosodium urate crystal-induced inflamed rats. Further, an acetic acid-induced writhing test and tail immersion test were employed to screen for analgesic effects, yeast-induced pyrexia was used to test for antipyretic effects, and gastric ulceration was used to evaluate ulcerogenic effects.. A significant increase in paw edema, lysosomal enzyme activity and lipid peroxidation levels was observed in monosodium urate crystal-induced rats, whereas activities of enzymic antioxidants were found to be decreased when compared to control rats. Nevertheless, treatment with p-Coumaric acid (100 mg/kg b.wt) significantly reverted the altered physical and biochemical parameters back to near normal levels, as evidenced by the histopathology of the ankle joints. In addition, p-Coumaric acid also exhibited potent analgesic and antipyretic effects devoid of any adverse impact on gastric mucosa.. The results of this study reveal the potential anti-inflammatory effect of p-Coumaric acid against monosodium urate crystal-induced inflammation in rats.

Topics: Acetic Acid; Acid Phosphatase; Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; beta-Glucosidase; Catalase; Coumaric Acids; Diet; Female; Fever; Glucuronidase; Hexosaminidases; Inflammation; Lipid Peroxidation; Male; Pain; Propionates; Rats; Rats, Wistar; Saccharomyces cerevisiae; Superoxide Dismutase; Uric Acid

In recent years, a significant number of metabolites with potent anti-inflammatory properties have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we isolated 11-epi-sinulariolide acetate (Ya-s11), a cembrane-type compound with anti-inflammatory effects, from the Formosa soft coral Sinularia querciformis. Preliminary screening revealed that Ya-s11 significantly inhibited the expression of the proinflammatory proteins induced nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated murine macrophages. We also examined the therapeutic effects of Ya-s11 on adjuvant-induced arthritis (AIA) in female Lewis rats, which demonstrate features similar to human rheumatoid arthritis (RA). Animal experiments revealed that Ya-s11 (subcutaneously 9 mg/kg once every 2 days from day 7 to day 28 postimmunization) significantly inhibited AIA characteristics. Moreover, Ya-s11 also attenuated protein expression of cathepsin K, matrix metalloproteinases-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor-α (TNF-α) in ankle tissues of AIA-rats. Based on its attenuation of the expression of proinflammatory proteins and disease progression in AIA rats, the marine-derived compound Ya-s11 may serve as a useful therapeutic agent for the treatment of RA.

Topics: Acid Phosphatase; Animals; Anthozoa; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Bone Resorption; Cathepsin K; Diterpenes; Drug Administration Schedule; Female; Gene Expression; Hindlimb; Inflammation; Injections, Subcutaneous; Isoenzymes; Matrix Metalloproteinase 9; Rats; Rats, Inbred Lew; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

In this study, chitosan-atorvastatin (Chi-AT) conjugate was immobilized onto the surfaces of titanium substrates to reduce inflammation responses and improve cytocompatibility. Polydopamine film was initially formed onto the titanium surfaces as the intermediate layer for the successful immobilization of Chi-AT, which was confirmed by scanning electron microscopy, X-ray photoelectron spectroscopy, and contact angle measurements, respectively. Endothelial cells grown onto Chi-AT immobilized titanium substrates displayed significantly higher (p < 0.01) cell viability and statistically lower (p < 0.01) lactate dehydrogenase production than those of native titanium substrates (control) after culture for 4 days and 7 days, respectively. Furthermore, macrophages cells cultured onto Chi-AT immobilized titanium substrates demonstrated significantly lower (p < 0.01) production levels of nitric oxide, acid phosphatase, reactive oxygen species, pro-inflammatory cytokines of tumor necrosis factor α, and interleukin-1 β than those of controls. All results indicated that the immobilization of Chi-AT conjugate onto titanium substrates was beneficial for improving their cytocompatibility and inhibiting pro-inflammatory responses. The study thus presents an alternative to fabricate bio-functionalized titanium-based implants for further clinical application.

Topics: Acid Phosphatase; Animals; Atorvastatin; Biocompatible Materials; Cells, Immobilized; Chitosan; Cytokines; Dogs; Fluorescent Antibody Technique; Heptanoic Acids; Human Umbilical Vein Endothelial Cells; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; L-Lactate Dehydrogenase; Macrophages; Magnetic Resonance Spectroscopy; Microscopy, Electron, Scanning; Nitric Oxide; Proteins; Pyrroles; Reactive Oxygen Species; Surface Properties; Titanium

Bones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the effects of propranolol in a model of experimental periodontal disease.. Rats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg·kg(-1) propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL-1β, TNF-α and cross-linked carboxyterminal telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion molecule 1 (ICAM-1), receptor activator of NF-κ B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro.. Propranolol at 0.1 and 5 mg·kg(-1) reduced the bone resorption as well as ICAM-1 and RANKL expression. However, only 0.1 mg·kg(-1) reduced IL-1β, TNF-α and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway and the expression of tartrate-resistant acid phosphatase (TRAP), cathepsin K and MMP-9.. Low doses of propranolol suppress bone resorption by inhibiting RANKL-mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.

Topics: Acid Phosphatase; Alveolar Bone Loss; Animals; Bone Resorption; Cathepsin K; Cell Differentiation; Cell Line; Collagen Type I; Dose-Response Relationship, Drug; Gene Expression; Gingiva; Hemodynamics; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; Isoenzymes; Male; Matrix Metalloproteinase 9; Mice; NFATC Transcription Factors; Osteoclasts; Peptides; Propranolol; RANK Ligand; Rats; Rats, Wistar; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Inflammation in the bone microenvironment stimulates osteoclast differentiation, resulting in uncoupling of resorption and formation. Mechanisms contributing to the inhibition of osteoblast function in inflammatory diseases, however, have not been elucidated. Rheumatoid arthritis (RA) is a prototype of an inflammatory arthritis that results in focal loss of articular bone. The paucity of bone repair in inflammatory diseases such as RA raises compelling questions regarding the impact of inflammation on bone formation. The aim of this study was to establish the mechanisms by which inflammation regulates osteoblast activity.. We characterized an innovative variant of a murine model of arthritis in which inflammation is induced in C57BL/6J mice by transfer of arthritogenic K/BxN serum and allowed to resolve.. In the setting of resolving inflammation, bone resorption ceased and appositional osteoblast-mediated bone formation was induced, resulting in repair of eroded bone. Resolution of inflammation was accompanied by striking changes in the expression of regulators of the Wnt/β-catenin pathway, which is critical for osteoblast differentiation and function. Down-regulation of the Wnt antagonists secreted frizzled-related protein 1 (sFRP1) and sFRP2 during the resolution phase paralleled induction of the anabolic and pro-matrix mineralization factors Wnt10b and DKK2, demonstrating the role of inflammation in regulating Wnt signaling.. Repair of articular bone erosion occurs in the setting of resolving inflammation, accompanied by alterations in the Wnt signaling pathway. These data imply that in inflammatory diseases that result in persistent articular bone loss, strict control of inflammation may not be achieved and may be essential for the generation of an anabolic microenvironment that supports bone formation and repair.

Topics: Acid Phosphatase; Animals; Arthritis, Experimental; Bone Regeneration; Follistatin-Related Proteins; Inflammation; Intercellular Signaling Peptides and Proteins; Isoenzymes; Joints; Mice; Mice, Inbred C57BL; Mice, Transgenic; Osteoblasts; Osteoclasts; Osteogenesis; Tartrate-Resistant Acid Phosphatase; Wnt Proteins; Wnt Signaling Pathway

Using receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation on RAW264.7 as a screening tool; we synthesize and identify small-molecule inhibitors preserving immunomodulatory effects as therapeutics for rheumatoid arthritis.. Differentiation into osteoclast-like cells was examined by tartrate-resistant acid phosphatase (TRAP) staining and expression of osteoclast differentiation markers. Collagen-induced arthritis (CIA) mice were administered test articles by gavages to assess its efficacy. Then clinical, histological, and biochemical parameters were assessed to determine the effects of N-(4-chloro-2-fluorophenyl)-2-hydroxybenzamide (NDMC101) on synovial inflammation and bone erosion by hematoxlin and eosin staining and Enzyme-linked immunosorbent assay (ELISA).. NDMC101 markedly inhibited RANKL-induced formation of TRAP+ multinucleated cells in RAW264.7 and bone marrow macrophage cells (BMMs). Moreover, pit formation assay showed that NDMC101 significantly reduced the bone-resorbing activity of mature osteoclasts. In CIA mice, oral administration of NDMC101 reduced arthritic index and mitigated bone erosion. Serum TNF-α and IL-1β concentrations in these mice were decreased significantly at the higher dose of 62.5 mg/kg.. Screening of our chemical library, our findings suggest that NDMC101 inhibits osteoclastogenesis which also ameliorates paw swelling and inflammatory bone destruction. Its efficacy is associated with the inhibition of such transcription factors as NF-κB and NFATc1 as well as multiple protein kinases, including p38, ERK, and JNK. There results guarantee further clinical tests of NDMC101 for its therapeutic potential in the treatment of inflammation-induced bone diseases.

Topics: Acid Phosphatase; Animals; Arthritis, Experimental; Benzamides; Cell Differentiation; Cell Line; Collagen; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation; Inflammation; Interleukin-1beta; Isoenzymes; JNK Mitogen-Activated Protein Kinases; Macrophages; Mice; Mice, Inbred DBA; NF-kappa B; NFATC Transcription Factors; Osteoclasts; p38 Mitogen-Activated Protein Kinases; RANK Ligand; Synovial Membrane; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by bone erosion and cartilage destruction in the joints. Many of the conventional antiarthritic drugs are effective in suppressing inflammation, but they do not offer protection against bone damage. Furthermore, the prolonged use of these drugs is associated with severe adverse reactions. Thus, new therapeutic agents that can control both inflammation and bone damage but with minimal side effects are sought. Celastrus is a Chinese herb that has been used for centuries in folk medicine for the treatment of various inflammatory diseases. However, its utility for protection against inflammation-induced bone damage in arthritis and the mechanisms involved therein have not been examined. We tested celastrus and its bioactive component celastrol for this attribute in the adjuvant-induced arthritis model of RA. The treatment of arthritic rats with celastrus/celastrol suppressed inflammatory arthritis and reduced bone and cartilage damage in the joints as demonstrated by histology and bone histomorphometry. The protective effects against bone damage are mediated primarily via the inhibition of defined mediators of osteoclastic bone remodeling (e.g. receptor activator of nuclear factor-κB ligand (RANKL)), the deviation of RANKL/osteoprotegerin ratio in favor of antiosteoclastic activity, and the reduction in osteoclast numbers. Furthermore, both the upstream inducers (proinflammatory cytokines) and the downstream effectors (MMP-9) of the osteoclastogenic mediators were altered. Thus, celastrus and celastrol controlled inflammation-induced bone damage by modulating the osteoimmune cross-talk. These natural products deserve further consideration and evaluation as adjuncts to conventional therapy for RA.

Topics: 3T3 Cells; Acid Phosphatase; Animals; Arthritis; Autoimmune Diseases; Bone and Bones; Celastrus; Cell Line; Fibroblasts; Immune System; Inflammation; Isoenzymes; Macrophages; Mice; Pentacyclic Triterpenes; Plant Extracts; Rats; Rats, Inbred Lew; Synovial Membrane; Tartrate-Resistant Acid Phosphatase; Triterpenes

The p38 mitogen-activated protein kinase (p38 MAPK) pathway is involved in the osteoclast differentiation. The aim of the study was to investigate whether SB203580, a p38 MAPK inhibitor, inhibits wear-debris-induced inflammatory osteolysis in mice. Forty-five mice were implanted with calvaria bone from syngeneic littermates; then, titanium (Ti) particles were injected into established air pouches to provoke inflammatory osteolysis. At 14 days after bone/Ti implantation, pouch membranes with intact bone implants underwent histological and molecular analysis. SB203580 had less effect on MMP-9 and TNF-α expression under wear-debris-induced conditions. SB203580, by inhibiting the expression of p38 MAPK and phospho-p38 MAPK, inhibited Ti particle wear-debris-induced inflammatory osteolysis. It also remarkably decreased the number of tartrate-resistant acid phosphatase positive cells in Ti-particle-induced pouch tissues. Results suggest that p38 MAPK may be critical in a murine osteolysis model. SB203580 may notably inhibit wear-debris-induced inflammatory osteolysis by down-regulating expression of MMP-9 and TNF-α via the p38 MAPK pathway.

Topics: Acid Phosphatase; Animals; Bone and Bones; Down-Regulation; Enzyme Inhibitors; Female; Imidazoles; Inflammation; Isoenzymes; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Osteoclasts; Osteolysis; p38 Mitogen-Activated Protein Kinases; Pyridines; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Titanium; Tumor Necrosis Factor-alpha

Articular cartilage degeneration and inflammation are the hallmark of progressive arthritis and is the leading cause of disability in 10-15% of middle aged individuals across the world. Cartilage and synovium are mainly degraded by either enzymatic or non-enzymatic ways. Matrix metalloproteinases (MMPs), hyaluronidases (HAases) and aggrecanases are the enzymatic mediators and inflammatory cytokines and reactive oxygen species being non-enzymatic mediators. In addition, MMPs and HAases generated end-products act as inflammation inducers via CD44 and TLR-4 receptors involved NF-κB pathway. Although several drugs have been used to treat arthritis, numerous reports describe the side effects of these drugs that may turn fatal. On this account several medicinal plants and their isolated molecules have been involved in modern medicine strategies to fight against arthritis. In view of this, the present study investigated the antiarthritic potentiality of Crocin, a dietary colorant carotenoid isolated from stigma of Crocus sativus. Crocin effectively neutralized the augmented serum levels of enzymatic (MMP-13, MMP-3 and MMP-9 and HAases) and non-enzymatic (TNF-α, IL-1β, NF-κB, IL-6, COX-2, PGE(2) and ROS) inflammatory mediators. Further, Crocin re-established the arthritis altered antioxidant status of the system (GSH, SOD, CAT and GST). It also protected the bone resorption by inhibiting the elevated levels of bone joint exoglycosidases, cathepsin-D and tartrate resistant acid phosphatases. Taken together, Crocin revitalized the arthritis induced cartilage and bone deterioration along with inflammation and oxidative damage that could be accredited to its antioxidant nature. Thus, Crocin could be an effective antiarthritic agent which can equally nullify the arthritis associated secondary complication.

Topics: Acid Phosphatase; Animals; Antioxidants; Arthritis, Experimental; Blotting, Western; Bone Resorption; Carotenoids; Cartilage, Articular; Cathepsin D; Cytokines; Dietary Supplements; Glutathione; Hyaluronoglucosaminidase; Inflammation; Inflammation Mediators; Isoenzymes; Liver; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Rats; Rats, Wistar; Superoxide Dismutase; Tartrate-Resistant Acid Phosphatase

Osteoprotegerin (OPG), as an osteoclast antagonist, limits mineralised tissue resorption under physiological conditions. Previous work investigating OPG in a rat periodontal ligament (PDL) ankylosis model found no inhibitory effect on osteoclasts when OPG was administered at a dosage of 2.5mg/kg.. The object of this study was to determine whether dosages higher than 2.5 mg/kg of OPG were required to limit osteoclastic activity in an aseptic inflammatory model in rats.. Dry ice was applied for 15 minutes to the upper right first molar crown of eighteen, 8-week-old, male Sprague-Dawley rats. Three groups of 3 were injected with OPG at dosages of 2.5, 5.0 and 7.5 mg/kg of body weight immediately following the thermal insult. After 7 days, the rats were sacrificed and each maxilla processed for histological examination and stained for osteoclastic activity using tartrate-resistant acid phosphatase (TRAP). Osteoclast population numbers were estimated via light microscopy and results were analysed using a comparative mixed model statistical analysis.. Results showed OPG inhibited osteoclastic activity in a dose-dependent manner. From 2.5 mg/kg to 7.5 mg/kg, osteoclast populations were linearly reduced by 39.78% (p < 0.05). OPG did not appear to affect the inflammatory process and had varied efficacy in different regions of individual teeth.. Although osteoclastic activity reduced, it was not completely eliminated, perhaps because dosages were still inadequate, or additional factors might influence OPG and osteoclast activation in the aseptic inflammatory model.

Topics: Acid Phosphatase; Animals; Biomarkers; Cell Count; Disease Models, Animal; Dose-Response Relationship, Drug; Dry Ice; Freezing; Inflammation; Isoenzymes; Male; Maxilla; Molar; Necrosis; Odontoblasts; Osteoclasts; Osteoprotegerin; Rats; Rats, Sprague-Dawley; Root Resorption; Tartrate-Resistant Acid Phosphatase; Tooth Crown

We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sjögren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.

Topics: Acid Phosphatase; Animals; Autoimmunity; Bone Diseases, Developmental; Cattle; Chromosomes, Human, Pair 19; Female; Gene Expression Regulation; Humans; Inflammation; Interferon Type I; Isoenzymes; Lupus Erythematosus, Systemic; Male; Models, Molecular; Mutation; Mutation, Missense; Phenotype; Sclerosis; Tartrate-Resistant Acid Phosphatase

This study was undertaken to determine the association between serum tartrate-resistant acid phosphatase 5a (TRACP5a) and cardiovascular disease (CVD) risk.. Four hundred patients were enrolled including, 291 asymptomatic subjects grouped by the number of traditional risk factors, 36 patients undergoing cardiac arteriography, 34 undergoing percutaneous cardiac intervention, and 39 with acute myocardial infarction. Serum was collected at baseline and, in arteriograpy and intervention groups, periodically for 1 week afterward. In addition to laboratory and clinical evaluation for risk assessment, serum TRACP5a, C-reactive protein (CRP) and interleukin-6 (IL-6) were determined.. All biomarkers rose with increasing CVD risk. Only serum TRACP5a, logCRP and cholesterol were elevated in symptomatic patients. Serum TRACP5a was higher in men and correlated with age, logCRP, logIL-6 and log-triglycerides, and in symptomatic patients, with the number of diseased coronary arteries. IL-6 and CRP showed acute phase responses, whereas TRACP5a did not change over 1 week after arteriography or intervention. After adjustment for all other variables and risk factors, TRACP5a and logCRP were the only biomarkers to associate with symptomatic disease. TRACP5a was more specific than CRP to predict myocardial infarction among all subjects.. Serum TRACP5a is a macrophage-derived inflammation marker associated with CVD risk, and with coronary vessel disease and its severity and may be a useful marker for screening and assessment of CVD risk.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Asymptomatic Diseases; Biomarkers; Cardiovascular Diseases; Female; Humans; Inflammation; Isoenzymes; Male; Middle Aged; Myocardial Infarction; Risk Factors; Tartrate-Resistant Acid Phosphatase; Young Adult

Bone-lining tissues contain a population of resident macrophages termed osteomacs that interact with osteoblasts in vivo and control mineralization in vitro. The role of osteomacs in bone repair was investigated using a mouse tibial bone injury model that heals primarily through intramembranous ossification and progresses through all major phases of stabilized fracture repair. Immunohistochemical studies revealed that at least two macrophage populations, F4/80(+) Mac-2(-/low) TRACP(-) osteomacs and F4/80(+) Mac-2(hi) TRACP(-) inflammatory macrophages, were present within the bone injury site and persisted throughout the healing time course. In vivo depletion of osteomacs/macrophages (either using the Mafia transgenic mouse model or clodronate liposome delivery) or osteoclasts (recombinant osteoprotegerin treatment) established that osteomacs were required for deposition of collagen type 1(+) (CT1(+)) matrix and bone mineralization in the tibial injury model, as assessed by quantitative immunohistology and micro-computed tomography. Conversely, administration of the macrophage growth factor colony-stimulating factor 1 (CSF-1) increased the number of osteomacs/macrophages at the injury site significantly with a concurrent increase in new CT1(+) matrix deposition and enhanced mineralization. This study establishes osteomacs as participants in intramembranous bone healing and as targets for primary anabolic bone therapies.

Topics: Acid Phosphatase; Animals; Bone Matrix; Calcification, Physiologic; Clodronic Acid; Disease Models, Animal; Inflammation; Isoenzymes; Liposomes; Macrophage Colony-Stimulating Factor; Macrophages; Membranes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Osteoblasts; Osteogenesis; Osteoprotegerin; Surface Properties; Tartrate-Resistant Acid Phosphatase; Tibia; Wound Healing

End-stage renal disease (ESRD) is often complicated by chronic inflammation and malnutrition. We tested whether serum tartrate-resistant acid phosphatase (TRACP) isoform 5a relates to other markers of inflammation in ESRD.. Predialysis serum was collected from 99 ESRD patients (51 male, 48 female) aged 55 +/- 15 years and a control group of 36 healthy subjects (8 male, 28 female) aged 43.2 +/- 10.5 years.. Serum TRACP 5a activity and protein, TRACP 5b activity and C-reactive protein (CRP) were estimated by in-house immunoassays. Commercial kits were used for serum bone-specific alkaline phosphatase, Ntelopeptides of Type I collagen, interleukin-6 (IL-6) and fetuin-A. Intact parathyroid hormone was determined by chemiluminescent assay. Albumin, cholesterol, triglycerides, ferritin and hemoglobin were compared to the hospital reference ranges. Bone mineral density (BMD) was measured at the heel in 69 patients and all control subjects and expressed as g/cm2 and age-corrected T-score.. Mean (median) levels of all serum markers were significantly elevated in ESRD except fetuin-A, which was significantly reduced. Mean BMD (g/cm2) was not different than control, but mean T-score was significantly reduced. TRACP 5a protein correlated with CRP, triglycerides and ferritin, but not with IL-6 or any other nutritional or bone markers or BMD. TRACP 5b activity correlated with all bone markers and BMD, but not with inflammation or nutritional markers.. Our findings suggest that TRACP 5a may be a useful marker to estimate the degree of inflammation in ESRD patients on chronic hemodialysis.

Topics: Acid Phosphatase; Adult; Albumins; Alkaline Phosphatase; alpha-Fetoproteins; Biomarkers; Bone Density; C-Reactive Protein; Case-Control Studies; Collagen Type I; Female; Humans; Inflammation; Interleukin-6; Isoenzymes; Kidney Failure, Chronic; Linear Models; Male; Middle Aged; Parathyroid Hormone; Protein Isoforms; Renal Dialysis; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase

Hydroxyapatite surface coatings of dental implants have been introduced to obtain more rapid and complete osteointegration. A possible complication associated with hydroxyapatite implant surface is the release of particles. Those particles may be phagocytosed by monocytes, the first cells to colonize the inflammatory sites. The activated monocytes produce cytokines that could cause osteoclast activation.. In order to establish the biological effect of particles released on monocyte differentiation to an osteoclast phenotype, we have used the murine monocyte/macrophage cell line, RAW 264.7 clone CRL-2278 cultured on a hydroxyapatite substrate. The direct action of hydroxyapatite on monocyte differentiation was examined using tartrate-resistant acid phosphatase (TRAP), immunohistochemistry and transmission electron microscopy (TEM) and Western Blot analysis.. The present study demonstrated that hydroxyapatite substrate might be able to induce a self-production of RANKL cytokine that directly stimulates a different behaviour in terms of phenotype expression from monocyte/macrophage lineage to mature and functional osteoclasts without the addition of exogenous factors.. These studies were designed to test a model in which osteoclasts could be formed from HA-activated monocytes via positive feedback elicited by RANKL, allowing for identification of innovative targets for therapeutic approaches.

Topics: Acid Phosphatase; Animals; Cell Culture Techniques; Cell Differentiation; Cell Line; Durapatite; Immunoblotting; Inflammation; Isoenzymes; Mice; Microscopy, Electron; Microscopy, Immunoelectron; Microscopy, Phase-Contrast; Monocytes; Osteoclasts; Tartrate-Resistant Acid Phosphatase

The purpose of this study was to determine whether macrophage depletion using clodronate liposomes diminishes wear-debris-induced inflammatory osteolysis in a murine osteolysis model. Ultra high molecular weight polyethylene (UHMWPE) particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. Macrophages were depleted by the intraperitoneal injection of clodronate liposome (2 mg) 2 days before bone implantation and re-injection every 3 days (1 mg) until the sacrifice of the mice. Mice without clodronate liposome therapy or treated with empty liposome as well as mice injected with saline alone were included in this study as controls. Pouch tissues were collected 14 days after bone implantation for molecular and histology analysis. Our findings indicated that (1) macrophage depletion in clodronate-liposome-treated mice was achieved, as illustrated by F4/80 immunostaining in both pouch and spleen tissues; (2) clodronate-liposome treatment significantly reduced UHMWPE-induced tissue inflammation, with diminished pouch membrane thickness, reduced inflammatory cellular infiltration, and lowered interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) expression; (3) clodronate-liposome treatment markedly reduced the number of TRAP(+) cells in pouch tissues and protected against bone collagen depletion. In conclusion, this study demonstrates that macrophage depletion using clodronate-liposome reduces UHMWPE particle-induced inflammatory osteolysis. This observation supports the hypothesis that macrophages contribute to the severity of UHMWPE particles induced inflammatory osteolysis, and suggest that macrophage depletion represents a viable therapeutic approach to the prevention and treatment of patients with aseptic loosening.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Resorption; Clodronic Acid; Collagen; Female; Implants, Experimental; Inflammation; Interleukin-1beta; Isoenzymes; Liposomes; Macrophages; Membranes; Mice; Mice, Inbred BALB C; Models, Animal; Molecular Weight; Osteoclasts; Osteolysis; Polyethylene; Protective Agents; Spleen; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

Large osteoclasts (>or=10 nuclei) predominate at sites of pathological bone resorption. We hypothesized this was related to increased resorptive activity of large osteoclasts and have demonstrated previously that larger osteoclasts are 8-fold more likely to be resorbing than small osteoclasts (2-5 nuclei). Here we ask whether these differences in resorptive activity can be explained by differences in expression of factors involved in osteoclast signaling, fusion, attachment, and matrix degradation. Authentic rabbit osteoclasts and osteoclasts derived from RAW264.7 cells showed similar increases in c-fms expression (1.7- to 1.8-fold) in large osteoclasts suggesting that RAW cells are a viable system for further analysis. We found 2- to 4.5-fold increases in the expression of the integrins alpha(v) and beta(3), the proteases proMMP9, matMMP9 and pro-cathepsinK, and in activating receptors RANK, IL-1R1, and TNFR1 in large osteoclasts. In contrast, small osteoclasts had higher expression of the fusion protein SIRPalpha1 and the decoy receptor IL-1R2. The higher expression of activation receptors and lower expression of IL-1R2 in large osteoclasts suggest they are hyperresponsive to extracellular factors. This is supported by the observation that the resorptive activity in large osteoclasts was more responsive to IL-1beta, and that this increased activity was inhibited by the IL-1 receptor antagonist, IL-1ra. This increased responsiveness of large osteoclasts to IL-1 may, in part, explain the pathological bone loss noted in inflammatory diseases. The heterogeneity in receptor expression and the differential response to cytokines and their antagonists could prove useful for selective inhibition of large osteoclasts actively engaged in pathological bone loss.

Topics: Acid Phosphatase; Animals; Arthritis; Cell Line; Cytokines; Enzyme Precursors; Immunoblotting; Inflammation; Integrin alpha1beta1; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Isoenzymes; Macrophage Colony-Stimulating Factor; Matrix Metalloproteinase 9; Mice; Osteoclasts; Rabbits; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptor, Macrophage Colony-Stimulating Factor; Receptors, Immunologic; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

Human serum contains 2 isoforms of type-5 tartrate-resistant acid phosphatase (TRACP): 5a and 5b. TRACP-5b is osteoclastic. Our goal was to determine if serum TRACP-5a could originate from inflammatory macrophages (MPhi). We stained 246 paraffin-embedded tissue samples for TRACP using monoclonal antibody 9C5 (mab9C5) to isoforms 5a and 5b and a novel mab220 specific to isoform 5a. CD68 and lysozyme were also stained. MPhi of chronic and granulomatous inflammation and in tissues that undergo strong antigenic stimulation were strongly positive for TRACP, more so with mab220 than with mab9C5. Noninflammatory MPhi in lymph node sinuses or germinal centers and red pulp MPhi of spleen were weak or negative for TRACP. Marginal zone lymphocytes and sebaceous glands of skin were weakly positive for TRACP. Tissue mast cells displayed strong TRACP staining. Neuroendocrine cells of gastrointestinal tissues were strongly immunoreactive with mab9C5 but negative with mab220. Restricted expression of TRACP primarily in inflammatory MPhi supports our hypothesis that circulating TRACP-5a could be a biomarker of chronic inflammatory disease activity.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Humans; Immunohistochemistry; Inflammation; Isoenzymes; Macrophages; Tartrate-Resistant Acid Phosphatase

Abatacept is the first in a new class of agents that selectively modulates T-cell activation by attenuating CD28-mediated co-stimulation. This study examined the effects of abatacept on disease development in a rat model of collagen-induced arthritis (CIA). The rats were treated with either abatacept (1mg/kg) or control IgG beginning at the time of induction of CIA. By day 16, significant paw swelling was observed in IgG-treated control animals that continued to increase, reaching a plateau on day 21. Prophylactic treatment with abatacept completely abrogated paw swelling throughout the study. Histopathology demonstrated a significant reduction in inflammation, cartilage destruction, bone resorption and pannus formation. Abatacept treatment resulted in 90% inhibition of circulating collagen-specific antibodies and decreased the serum expression of many cytokines and chemokines that were upregulated in diseased animals. Immunohistochemical analysis of the ankle joints demonstrated that interleukin-6 production was reduced in the tissues and the numbers of osteoclasts present in the joints were also decreased. Ankle microcomputer tomography (micro-CT) analyses dramatically demonstrated the protective effects of abatacept on bone destruction in these animals. Data presented here demonstrate that prophylactic administration of abatacept significantly inhibits the onset and progression of disease in a rat CIA model, with reductions in inflammation, inflammatory mediators, and bone and joint destruction.

Topics: Abatacept; Acid Phosphatase; Animals; Arthritis, Experimental; Autoantibodies; Bone and Bones; Bone Resorption; Collagen; Disease Models, Animal; Female; Immunoconjugates; Inflammation; Isoenzymes; Osteoclasts; Rats; Tarsal Joints; Tartrate-Resistant Acid Phosphatase

TNF-alpha is the dominant cytokine in inflammatory osteolysis. Using mice whose BM stromal cells and osteoclast precursors are chimeric for the presence of TNF receptors, we found that both cell types mediated the cytokine's osteoclastogenic properties. The greater contribution was made, however, by stromal cells that express the osteoclastogenic cytokine M-CSF. TNF-alpha stimulated M-CSF gene expression, in vivo, only in the presence of TNF-responsive stromal cells. M-CSF, in turn, induced the key osteoclastogenic cytokine receptor, receptor activator of NF-kappaB (RANK), in osteoclast precursors. In keeping with the proproliferative and survival properties of M-CSF, TNF-alpha enhanced osteoclast precursor number only in the presence of stromal cells bearing TNF receptors. To determine the clinical relevance of these observations, we induced inflammatory arthritis in wild-type mice and treated them with a mAb directed against the M-CSF receptor, c-Fms. Anti-c-Fms mAb selectively and completely arrested the profound pathological osteoclastogenesis attending this condition, the significance of which is reflected by similar blunting of the in vivo bone resorption marker tartrate-resistant acid phosphatase 5b (TRACP 5b). Confirming that inhibition of the M-CSF signaling pathway targets TNF-alpha, anti-c-Fms also completely arrested osteolysis in TNF-injected mice with nominal effect on macrophage number. M-CSF and its receptor, c-Fms, therefore present as candidate therapeutic targets in states of inflammatory bone erosion.

Topics: Acid Phosphatase; Animals; Antibodies, Monoclonal; Bone and Bones; Bone Marrow Cells; Bone Resorption; CD4 Antigens; CD8 Antigens; Cell Separation; Cytokines; Dose-Response Relationship, Drug; Female; Flow Cytometry; Gene Expression Regulation; Inflammation; Interleukin-1; Isoenzymes; Macrophage Colony-Stimulating Factor; Macrophages; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, SCID; Mice, Transgenic; NF-kappa B; Osteoclasts; Osteolysis; Rats; Receptor, Macrophage Colony-Stimulating Factor; Recombinant Fusion Proteins; RNA, Messenger; Signal Transduction; Stromal Cells; T-Lymphocytes; Tartrate-Resistant Acid Phosphatase; Time Factors; Tumor Necrosis Factor-alpha

This study evaluated the in vivo biocompatibility and biodegradation behavior of a novel polypyrrole (PPy)/poly(D,L-lactide) (PDLLA) composite and PPy-coated poly(D,L-lactide-co-glycolide) membranes. Test membranes were implanted subcutaneously in rats for 3-120 days. The biocompatibility was assessed by quantifying the alkaline and acid phosphatase secretion, the immunohistochemical staining of the ED-2-positive macrophages, and the histology at the tissue/material interface. The degradation was investigated using scanning electron microscopy. Pure PDLLA and poly(D,L-lactide-co-glycolide) membranes were used as references, whereas expanded polytetrafluoroethylene and a commercial styrene-butadiene rubber were used as controls. The enzyme activity of the PPy-containing specimens was shown to be similar to that of the references. The histological findings were consistent with the enzymatic results, showing a mild-to-moderate acute inflammation followed by a resolution of the inflammatory response with a decrease in inflammatory cells for each biodegradable membrane. The tissue reactions to the PPy, which was either in the form of nanoparticles or surface coating, were comparable to the response to the neighboring biodegradable materials. Elevated ED-2-positive macrophage populations appeared as early as day 3 in the loose connective tissue surrounding the implants. The density of these populations was related to the degree of inflammation. Scanning electron microscopy showed that the degradation of the PPy/PDLLA composite was not affected by the presence of PPy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biocompatible Materials; Biodegradation, Environmental; Collagen; Electric Conductivity; Fibrin; Immunohistochemistry; Inflammation; Lactic Acid; Macrophages; Male; Materials Testing; Membranes, Artificial; Microscopy, Electron, Scanning; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Polytetrafluoroethylene; Prostheses and Implants; Pyrroles; Rats; Rats, Sprague-Dawley; Sterilization; Tissue Fixation

Fluoride-resistant acid phosphatase (FRAP) has been suggested as an enzymatic marker for nociceptive primary afferent terminals in the spinal dorsal horn, however there has not been demonstrated a direct functional relation between FRAP activity and an increased nociceptive transmission. For this purpose, we quantitated FRAP activity in the spinal dorsal horn of the rat in a heat-induced cutaneous inflammatory model. Male Sprague-Dawley rats anaesthetised with thiopental were separated in two groups where the left hindpaw was submerged during 60 s either in water at room temperature (control group) or in water at 60 degrees C (inflammation group) which induce in this group a progressive hindpaw inflammation. After 8 h, the lumbar enlargement of the spinal cord was extracted, cut in slices and 1 mm micropunch fragments were obtained from the right and left dorsal horn. The activity of FRAP was determined using the Gomori colorimetric method and corrected by the protein concentrations. FRAP activity in the left dorsal horn was statistically higher than right dorsal horn in the inflammation group (3.05+/-0.54 versus 1.91+/-0.23 u/g per l; P<0.05). Also, FRAP activity from the left dorsal horn of the control and inflammation groups show a significant increase in the last group (3.05+/-0.54 versus 2.17+/-0.23 u/g per l; P<0.05). This results demonstrate that FRAP is not only an enzymatic marker for neuronal and fibre integrity of nociceptive primary afferents but also it is associated to the nociceptive afferent activation.

Topics: Acid Phosphatase; Animals; Fluorides; Functional Laterality; Hot Temperature; Inflammation; Male; Neurons, Afferent; Physical Stimulation; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Spinal Cord

Histological examination of 38 nodular formations extirpated from the site of vaccine administration to cats disclosed 25 cases of sarcoma and 13 of granuloma. Average age of the cats bearing sarcoma was 8.75 years whereas granuloma occurred at average age of 1.9 year. This age-relationship of the lesions, as well as their similar morphologic features indicated a progression of chronic inflammatory changes to tumors. Similar tumors were diagnosed in one cat with "posttraumatic ocular sarcoma" and in the uterus of female-cat with long-standing pyometra. These two cats were 15 and 8 years old, respectively. Experimental study of local reaction 21 days after administration of commercial, lipid-adjuvanted vaccine revealed in young cats (age 9 months) a reaction to immunogen, whereas in old animals (age 10 to 15 years) there was a reaction to foreign material. The data suggest that chronic inflammation and age-related immunodeficiency are instrumental in pathogenesis of the vaccine-associated sarcoma.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carboxylesterase; Cat Diseases; Cats; Female; Immunocompromised Host; Immunoenzyme Techniques; Inflammation; Male; Sarcoma; Soft Tissue Neoplasms; Vaccination

Electrically conductive polypyrrole is very attractive for tissue engineering because of its potential to modulate cellular activities through electrical stimulation. However, its in vivo behaviors have not been fully studied. This paper investigates the in vivo biocompatibility and biostability of PPy-coated polyester fabrics. Three PPy-coated fabrics were prepared using phosphonylation (PPy-Phos), plasma activation (PPy-Plas), and plasma activation plus heparin treatment (PPy-Plas-HE). Virgin and fluoropassivated fabrics (F-PET) were controls. The specimens were implanted subcutaneously in the back of rats for 3-90 days, then harvested and processed for enzymatic, histological, and morphological analyses. A noninvasive MRI method was used to continuously monitor the inflammation. The level of acid and alkaline phosphatase showed a similar or a less intensive cellular reaction by the PPy-coated fabrics, when compared to the controls. Histology supported the enzymatic results and showed a fast collagen infiltration at 28 days for the PPy-Phos fabric. MRI reported an overall decrease of inflammation over time, with the PPy-coated fabrics showing a similar or mild inflammation in contrast to the non-coated fabrics. PPy clusters and excessive PPy laminary coating on the PPy-Plas and PPy-Plas-HE were lost with the implantation. This experiment suggests a similar in vivo biocompatibility of the PPy-coated and noncoated polyester fabrics and the importance of achieving a thin, uniform PPy coating.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Collagen; Inflammation; Magnetic Resonance Imaging; Male; Materials Testing; Muscles; Polyesters; Polymers; Pyrroles; Rats; Rats, Sprague-Dawley; Textiles

The current study was undertaken to determine if the presence of titanium wear particulate deleteriously influences early osseointegration of posterolateral bone graft or disrupts an established posterolateral fusion mass.. Using an in vivo animal model to evaluate the effect(s) of titanium wear particulate on a posterolateral spinal arthrodesis based on serologic, histologic, and immunocytochemical analyses.. The effect of unintended wear particulate resulting from micromotion between the interconnection mechanisms in spinal instrumentation remains a clinical concern.. Thirty-four New Zealand White rabbits were randomized into two groups based on postoperative time periods of 2 months (Group 1, n = 14) and 4 months (Group 2, n = 20). Group 1 underwent a posterolateral arthrodesis at L5-L6 using tricortical iliac autograft or tricortical iliac autograft + titanium particulate. Group 2 received iliac autograft at the initial surgery and were reoperated on after 8 weeks and treated with posterolateral arthrodesis exposure alone or titanium particulate. Postoperative analysis included serologic quantification of systemic cytokines. Postmortem microradiographic, immunocytochemical, and histopathologic assessment of the intertransverse fusion mass quantified the extent of osteolysis, local pro-inflammatory cytokines, osteoclasts, and inflammatory infiltrates.. Serologic analysis of systemic cytokines indicated no significant differences in cytokine levels (P > 0.05) between the titanium or autograft treatments. Immunocytochemistry indicated increased levels of local cytokines (tumor necrosis factor-alpha) at the titanium-treated posterolateral arthrodesis sites at both time periods (P < 0.05). Osteoclast cell counts and regions of osteolytic resorption lacunas were higher in the titanium-treated versus autograft-alone groups (P < 0.05), and the extent of cellular apoptosis was markedly higher in the titanium-treated sites at both time intervals. Electron microscopy indicated definitive evidence of phagocytized titanium particles and foci of local, chronic, inflammatory changes in the titanium-treated sites.. Titanium particulate debris introduced at the level of a spinal arthrodesis elicits a cytokine-mediated particulate-induced response favoring pro-inflammatory infiltrates, increased expression of intracellular tumor necrosis factor-alpha, increased osteoclastic activity, and cellular apoptosis. The presence of titanium particulate debris, secondary to motion between spinal implants, may serve as the impetus for late-onset inflammatory-infectious complications and long-term osteolysis of an established posterolateral fusion mass in the clinical setting.

Topics: Acid Phosphatase; Animals; Apoptosis; Bone Transplantation; Cell Count; Cytokines; Ilium; Immunohistochemistry; Implants, Experimental; Inflammation; Lumbar Vertebrae; Macrophages; Models, Animal; Osteoclasts; Osteolysis; Particle Size; Rabbits; Radiography; Spinal Fusion; Titanium; Treatment Outcome; Tumor Necrosis Factor-alpha

Our objective was to evaluate the significance and source of serum tartrate-resistant acid phosphatase (TRACP) in patients with rheumatoid arthritis (RA).. Thirty-five RA, 32 osteoarthritis (OA) and 16 control subjects were studied. Serum TRACP-5b activity and total TRACP protein were determined by immunoassay. TRACP isoforms were analyzed by non-denaturing polyacrylamide gel electrophoresis (PAGE). Serum bone alkaline phosphatase (BAP), cross-linked N-terminal telopeptides (NTx), and C-terminal telopeptides (ICTP) of type I collagen were estimated as markers of bone turnover. C-reactive protein (CRP) was measured as a marker of chronic inflammation. Macrophages and dendritic cells (DC) were developed from peripheral blood monocytes. Cell lysates and culture supernatants were analyzed for TRACP isoforms by immunoassay and PAGE.. In RA, mean TRACP-5b activity was normal, but median total TRACP protein was increased twofold (p<0.001). In OA, TRACP-5b activity and protein were normal. In RA, TRACP-5b activity correlated weakly with ICTP (r=0.56) while TRACP protein levels correlated weakly with NTx (r=0.43). Additionally, TRACP protein, but not TRACP-5b activity correlated significantly with CRP (r=0.42). Macrophage and DC lysates contained TRACP-5b, while tissue culture supernatants contained TRACP-5a.. Increased total TRACP protein in RA sera was probably due to TRACP-5a and not derived from osteoclasts. Rather, it could be a secreted product of inflammatory macrophages and DC.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cells, Cultured; Dendritic Cells; Electrophoresis, Polyacrylamide Gel; Humans; Immunoassay; Inflammation; Isoenzymes; Macrophages; Middle Aged; Osteoarthritis; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase (TRAP) is a lysosomal di-iron protein of mononuclear phagocytes and osteoclasts. Hitherto, no role for the enzyme in immunity has been identified; however, knockout mice lacking TRAP have a skeletal phenotype caused by an intrinsic osteoclast defect. To investigate a putative function for TRAP in macrophages (Mphi), we investigated proinflammatory responses and systemic microbial clearance in knockout mice compared with age- and gender-matched congenic wild-type mice. Phorbol 12-myristate 13-acetate (PMA)-stimulated and interferon-gamma (IFN-gamma)-induced superoxide formation was enhanced in peritoneal Mphi lacking TRAP; nitrite production in response to stimulation with lipopolysaccharide (LPS) and IFN-gamma was also increased. In addition, secretion of the proinflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-12, was significantly greater in TRAP-deficient Mphi when stimulated with LPS, with or without addition of either TNF-alpha or IFN-gamma. The activity of tartrate-sensitive (lysosomal) acid phosphatase was increased in Mphi from the knockout mice but activities of the lysosomal hydrolases N-acetyl beta-glucosaminidase and acid beta-glucuronidase were unchanged, indicating selective activation of compensatory acid phosphatase activity. Evidence of impaired Mphi function in vivo was obtained in TRAP knockout mice, which showed delayed clearance of the microbial pathogen, Staphylococcus aureus, after sublethal intraperitoneal inoculation. After microbial challenge, peritoneal exudates obtained from TRAP knockout mice had a reduced population of Mphi. As peritoneal Mphi and neutrophils lacking TRAP were able to phagocytose and kill S. aureus normally in vitro, TRAP may directly or indirectly influence recruitment of Mphi to sites of microbial invasion. Our study shows that TRAP participates in the inflammatory response of the Mphi and influences effector signalling pathways in innate immunity.

Topics: Acid Phosphatase; Animals; Bone Marrow; Cytokines; Female; Free Radicals; Immunophenotyping; Inflammation; Isoenzymes; Lysosomes; Macrophages; Macrophages, Peritoneal; Male; Mice; Mice, Knockout; Phagocytosis; Staphylococcal Infections; Staphylococcus aureus; Superoxides; Tartrate-Resistant Acid Phosphatase

The present study was undertaken to validate the benefits of a fluoropolymer treatment on the biostability, inflammatory response, and healing characteristics of a polyester mesh used for hernia repair, the Fluoromesh, as compared to a commercial monofilament-knit polypropylene mesh, Marlex, used as the control. Both were implanted for the repair of surgically induced abdominal hernias in piglets for prescheduled durations of implantation of 4, 15, and 60 days. The mesh and surrounding tissue were harvested at the sacrifice for the bursting strength and inflammatory response measurements in terms of alkaline and acid phosphatase secretion in the tissue, and for histological observations of the healing sequence and tissue thickness measurements by histomorphometric techniques. After cleaning to remove adherent tissue, the presence of the fluoropolymer at the surface of the mesh was detected using SEM and ESCA. The results demonstrated greater mechanical reinforcement and tissue development for the Fluoromesh than for the polypropylene mesh. The healing performance of the Fluoromesh was attributed to a more intense chronic inflammatory reaction early after implantation that stimulated significantly greater tissue ingrowth and integration. The concentration of fluoropolymer at the surface of the mesh was masked as a result of biological species adsorption. Textile analysis revealed that the Fluoromesh was dimensionally more stable in vivo than the polypropylene control mesh, which demonstrated stretching in the weft direction and shrinking in the warp direction during implantation.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biocompatible Materials; Female; Fluorocarbon Polymers; Hernia, Inguinal; Inflammation; Materials Testing; Microscopy, Electron, Scanning; Surgical Mesh; Swine; Wound Healing

Toxoplasma antigen and Toxoplasma immune complex were shown to induce increased production and release of acid hydrolases from macrophage cell line P388D in a concentration-dependent manner. Antigen concentrations of 10-50 microg/ml gave a 2-4-fold increase in the activities of acid proteinase, acid phosphatase, and phospholipase A2 compared with control cells without antigen. Results were similar for immune complex concentrations of 30-80 microg/ml compared with controls. No significant lactate dehydrogenase activity was detected in the culture medium, indicating that enzyme release was selective and not due to cell death. These results suggest that increased release of acid hydrolases may play a role in the inflammatory lesions observed in Toxoplasma encephalitis.

Topics: Acid Anhydride Hydrolases; Acid Phosphatase; Animals; Antigens, Protozoan; Cell Line; Cells, Cultured; Fibroblasts; Humans; Inflammation; Kinetics; Macrophages, Peritoneal; Toxoplasma; Toxoplasmosis

The present investigation explored the possible venom neutralizing effect of a pure compound (2-hydroxy-4-methoxy benzoic acid) isolated and purified from the methanolic root extract of Hemidesmus indicus R.Rr. 2-OH-4-MeO benzoic acid possessed potent anti-inflammatory, antipyretic and antioxidant properties. The compound effectively neutralized inflammation induced by Vipera russelli venom in male albino mice and reduced cotton pellet-induced granuloma in rats. The compound produced a significant fall in body temperature in yeast-induced pyrexia in rats but did not change the normothermic body temperature. The compound effectively neutralized viper venom-induced changes in serum phosphatase and transaminase activity in male albino rats. It also neutralized free radical formation as estimated by TBAPS and superoxide dismutase activities. The antisnake venom activity of the pure compound is partly mediated through the above physiological process.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Anti-Inflammatory Agents; Benzoates; Body Temperature; Daboia; Free Radicals; Guinea Pigs; Inflammation; Lipid Peroxidation; Male; Medicine, Ayurvedic; Mice; Plant Extracts; Plant Roots; Plants, Medicinal; Rats; Viper Venoms

We have shown that normal C57BL/6J mice are moderately resistant to infection with murine cytomegalovirus (MCMV) and that this resistance is impaired by prior infection with LP-BM5 MuLV, which causes a disease (MAIDS) similar to early HIV-induced disease. This study investigates macrophage function in MAIDS+ mice challenged with MCMV. MAIDS reduces the influx of cells into the peritoneal cavity seen in normal C57BL/6J mice 6 days after MCMV infection. The infiltrates contained cells that resembled activated macrophages, as they took up colloidal gold, expressed the macrophage marker Mac-1, had high levels of acid phosphatase activity, and were lymphocytostatic when co-cultured with activated T cells. MAIDS+ mice had a higher percentage of cells able to take up colloidal gold and higher acid phosphatase activity per cell. The cells were also more lymphocytostatic and produced higher levels of interleukin-1 and tumor necrosis factor-alpha on days 4 and 6 after MCMV infection. Hence, MAIDS enhances baseline and induced macrophage activity, but depresses infiltration into the site of inflammation.

Topics: Acid Phosphatase; Animals; Cells, Cultured; Coculture Techniques; Cytomegalovirus; Cytomegalovirus Infections; Female; Flow Cytometry; Inflammation; Interleukin-1; Lymphocyte Activation; Macrophage Activation; Macrophage-1 Antigen; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Murine Acquired Immunodeficiency Syndrome; T-Lymphocytes; Time Factors; Tumor Necrosis Factor-alpha

Immunohistochemical studies were done on formalin-fixed, paraffin-embedded tissues to evaluate the specificity of a newly developed monoclonal antibody (9C5) against tartrate-resistant acid phosphatase. Sections from 195 specimens were examined, which included 33 types of tissues/organs. These tissues included normal, inflammatory, and neoplastic processes. Neoplastic tissues from 14 patients with hairy cell leukemia served as positive controls. Epitope enhancement was accomplished either by microwave irradiation in citrate buffer or by boiling in water followed by trypsin digestion. Tissues were reacted with monoclonal antibody 9C5 and stained with either the avidin-biotin peroxidase method or the alkaline phosphatase anti-alkaline phosphatase method. The hairy cells of all cases of hairy cell leukemia reacted positively with 9C5. Other positively stained cells included osteoclasts, activated macrophages and giant cells. Immunohistochemical studies with 9C5, when interpreted within the context of the specificity of this antibody, are useful for the diagnosis and assessment of treatment results for hairy cell leukemia. Monoclonal antibody 9C5 also may be useful as a marker for osteoclasts and the activated macrophages and for the diagnosis of disorders involved by these cells.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antibody Specificity; Biomarkers, Tumor; Hematopoiesis; Humans; Immunohistochemistry; Inflammation; Isoenzymes; Kupffer Cells; Leukemia, Hairy Cell; Macrophages; Neoplasms; Reference Values; Tartrate-Resistant Acid Phosphatase

Pharmacokinetic and pharmacodynamic variables of flunixin were studied in calves after IV administration of the drug at a dose rate of 2.2 mg/kg of body weight. The anti-inflammatory properties of flunixin were investigated, using a model of acute inflammation; this involved surgically implanting tissue cages at subcutaneous sites and stimulating the tissue cage granulation tissue by intracavitary injection of carrageenan. The actions of flunixin on exudate concentrations of several substances related to the inflammatory process, including proteases (metalloprotease [active and total] and cysteine and serine proteases), enzymes (lactate dehydrogenase, acid phosphatase, and beta-glucuronidase [beta-glu]), eicosanoid (prostaglandin E2 [PGE2], leukotriene B4, and serum thromboxane B2 [TXB2]) concentrations, and bradykinin (BK)-induced edema, were investigated. Flunixin had a long elimination half-life--6.87 +/- 0.49 hours--and volume of distribution was 2.11 +/- 0.37 L/kg, indicating extensive distribution of the drug in the body. Body clearance was 0.20 +/- 0.03 L/kg/h. Flunixin exerted inhibitory effects on serum TXB2 and exudate PGE2 concentrations, beta-glu activity, and BK-induced swelling. Other enzymes and inflammatory mediators were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Clonixin; Cross-Over Studies; Cysteine Endopeptidases; Exudates and Transudates; Glucuronidase; Inflammation; L-Lactate Dehydrogenase; Lysosomes; Metabolic Clearance Rate; Metalloendopeptidases; Models, Biological; Serine Endopeptidases

Zymosan-induced stimulation of mononuclear phagocyte system was used as a model for study of inflammation in vivo. Zymosan administration to mice was followed by increase of macrophage enzyme markers beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activity in liver and serum. Serum acid glucosidases secretion occurred both after macrophage stimulation by zymosan and macrophage depression induced by GdCl3. Liver granulomatous inflammation resulted increased activity of liver cathepsin B and cathepsin L. There was no changes of cysteine proteinases studied in the case of macrophage depression by GdCl3. The role of lysosomal enzymes secretion in macrophage stimulation and inflammation was discussed.

Topics: Acid Phosphatase; Animals; Cathepsin B; Cathepsin L; Cathepsins; Cysteine Endopeptidases; Endopeptidases; Gadolinium; Glycoside Hydrolases; Inflammation; Kinetics; Liver; Lysosomes; Macrophages; Male; Mice; Mice, Inbred CBA; Zymosan

Liver and serum lysosomal enzymes (acid glucosidases and cysteine proteinases) during zymosan-induced stimulation of MPS or MPR depression induced by GdCl3 have been studied. Zymosan was used as a model for study of inflammation in vivo. The development of inflammation induced by zymosan was followed by increase activity of macrophage activation markers - beta-N-acetylglucosaminidase (NAGlu) and beta-N-acetylgalactosaminidase (NAGal) in liver and serum. There was enhance of liver cysteine proteinases activity. Similar, less prominent (partly) data were obtained during macrophage depression induced by GdCl3.

Topics: Acid Phosphatase; Animals; Cysteine Endopeptidases; Gadolinium; Glycoside Hydrolases; Inflammation; Kinetics; Liver; Lysosomes; Male; Mice; Mice, Inbred CBA; Zymosan

The purpose of this study was to quantitate biochemically and to localize histochemically the proteases cathepsin B (Cath B), dipeptidyl peptidase I (DPP I), and dipeptidyl peptidase II (DPP II) in experimental pulmonary granulomatosis and fibrosis. These were compared to the prototypical lysosomal hydrolase acid phosphatase (AP). Granulomatosis was induced by the intravenous injection of complete Freund's adjuvant (CFA, 0.2 ml) and fibrosis was induced by the intratracheal instillation of bleomycin sulfate (1 unit) in rats (Wistar, 200 g). Total Cath B, DPP I, and AP activities were markedly elevated over control values five days following both treatments when expressed as activity per lung or as specific activity per milligram protein or milligram DNA. By 14 and 28 days, total activity was elevated for all three enzymes, and activity per milligram DNA remained elevated for Cath B following both treatments and for DPP I 28 days following CFA treatment. Total lung activity of DPP II was significantly elevated at 28 days for both treatments. Histochemical staining indicated that these changes are due, in part, to the influx of inflammatory monocytes and their maturation to macrophages. This study provides a basis for examining the role of these proteases in connective tissue matrix injury during inflammatory processes in the lungs.

Topics: Acid Phosphatase; Adjuvants, Immunologic; Animals; Bleomycin; Cathepsin B; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Granuloma; Histocytochemistry; Inflammation; Lung Diseases; Male; Pulmonary Fibrosis; Rats; Time Factors

Female BALB/cJ (resistant), C3H/HeJ (intermediate resistant), and C3H/HeDub (susceptible) inbred mice, 4-5 wk old, were infected with Taenia taeniaeformis. Liver sections were stained for the enzymes acid phosphatase, beta-glucuronidase, and peroxidase. Eosinophils present around the parasite were identified by the ethanolic Congo red method. Possible gross changes in lipid metabolism in the hepatocytes surrounding the parasite were investigated with the Sudan black B method. The results of observations made by light microscopy were: (1) beta-glucuronidase activity above background levels was observed only in the hepatocytes around the parasite in BALB/cJ mice at 4, 5, and 6 days postinfection (PI); no reaction was observed in the other 2 strains of mice studied; (2) acid phosphatase activity was very strong at 2, 3, and 4 in the 3 strains of mice while this reactivity was weak at 5 and 6 days PI; (3) the cytoplasm of the hepatocytes around the metacestode stained more heavily with Sudan black B than other hepatocytes; and (4) the presence of eosinophils appearing at 3 days PI around the parasite in all 3 strains of mice was demonstrated by staining with Sudan black B, the substrate of peroxidase, and Congo red. Infected C3H/HeJ and BALB/cJ mice had higher numbers of liver eosinophils than infected C3H/HeDub mice throughout the observation time. The present results suggest 2 conclusions: (1) a parasite-liver interaction occurs as is evident by hepatocyte changes in beta-glucuronidase activity and Sudan black B staining, and (2) resistance to the early stages of T. taeniaeformis is associated with the appearance of eosinophils.

Topics: Acid Phosphatase; Animals; Azo Compounds; Congo Red; Disease Susceptibility; Eosinophils; Female; Glucuronidase; Histocytochemistry; Immunity, Innate; Inflammation; Leukocyte Count; Liver; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Naphthalenes; Peroxidase; Staining and Labeling; Taeniasis

The biochemical basis of the hepatitis-like liver injury produced by D(+)-galactosamine in rats is well-established and is linked to depletion of uridine nucleotides within parenchymal cells. However, the prominent inflammatory response that accompanies this lesion in vivo has been largely overlooked as a component of the hepatic damage. This study examines the cellular components of the inflammatory infiltrate of galactosamine-induced liver injury over time using histochemical and ultrastructural techniques. By 12 h after toxin administration, the infiltrate consisted largely of neutrophils and recently-mobilized monocytes. By 24 to 48 h after the toxin, when hepatocellular necrosis was maximal, few neutrophils were found in the infiltrate. At these times, the infiltrate consisted almost exclusively of large phagocytic cells, histochemically and morphologically consistent with active tissue macrophages apparently derived from circulating monocytes. The extent of the inflammatory response to this experimental hepatotoxin suggests that effects on the generation and development of the inflammatory response should be considered for treatments reported to alter the intrinsic hepatotoxicity of galactosamine.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Chemical and Drug Induced Liver Injury; Galactosamine; Inflammation; Lectins; Liver; Male; Microscopy, Electron; Monocytes; Neutrophils; Peanut Agglutinin; Rats; Rats, Inbred Strains

A series of human multinucleate giant cells (MGCs) of the endocytotic type were studied using enzyme histochemical methods for dehydrogenases, glycosidases, phosphatases, and peptidases. Several enzyme patterns were found. The subgroup of MGCs associated with inflammatory granulomatous processes (sarcoidosis, granulomatous myositis, familial granulomatosis, lymphogranuloma, granulomatous cholangitis) was characterized by high activities of nonspecific esterase (NE) and tartrate-sensitive acid phosphatase (AcPase-Ts). There was no detectable activity of peptidases or tartrate-resistant isoenzyme of acid phosphatase (AcPase-Tr). This enzyme equipment was indistinguishable from that in mononuclear precursors in the granulomas. The other MGCs of the series displayed enzyme patterns substantially different from their monocytic precursors (blood monocytes and Langerhans cells). The subgroup of foreign body associated MGCs (resorption of fat, keratin, and suture material) was characterized by high activities of NE, AcPase-Tr, and greatly variable activities of both peptidases studied. The latter lacked predilection for certain subcellular regions. The subgroup of osteoclasts and so-called giant cell tumours (osteoclastoma, giant cell tumour of soft parts, giant cell epulis of peripheral, and central types) displayed very low activity of NE, high activity of AcPase-Tr, and strong activities of peptidases. The latter were localized near the surface membrane of the polykarya. MGCs in histiocytosis X (HX) differed from the previous group by higher values of NE in average. All MGC types had common denominator in the absence of alkaline phosphatase activity, on average intense dehydrogenase activities, mostly low beta-glucuronidase and highly variable alpha-mannosidase activities. The enzyme pattern heterogeneity is discussed with regard to the phenomenon of enzyme induction and depression occurring in course of polykaryon production. The variability of phenomenon may reflect reactive adaptation to varying functional demands imposed on MGCs under different conditions.

Topics: Acid Phosphatase; Aminopeptidases; Carboxylesterase; Carboxylic Ester Hydrolases; Carcinoma; CD13 Antigens; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Endocytosis; Granuloma; Humans; Inflammation; Isoenzymes; Osteoclasts

An experimental subcutaneous inflammation was produced in guinea pigs with peripheral blood eosinophilia. The eosinophilia resulted from two subsequent infections with Trichinella spiralis larvae. One group of guinea pigs served as non-infected control. Inflammation was induced by carrageenan, bradykinin, histamine, platelet activating factor and eosinophilotactic factors of lymphocytic or neutrophilic origin. Whereas in the control group no eosinophil granulocytic response was observed, this response was seen in the group with peripheral blood eosinophilia. The inflammatory substances and mediators (carrageenan, bradykinin, histamine, platelet activating factor) did not attract eosinophils alone, but also neutrophils. Under peripheral blood eosinophilia within the time course of the inflammatory reaction a second emigration with a shifted neutrophil/eosinophil ratio in favour of eosinophils was found. This could be due to a generation of chemoattractants by the injected substances themselves or more probably, by already emigrated granulocytes. Neither histamine, bradykinin, carrageenan, nor the eosinophilotactic factors (ECF's) in the concentrations used did release the cytotoxic major basic protein from eosinophils. Platelet activating factor exhibited a release of major basic protein from some eosinophils but no release of the peroxidase under our experimental conditions. The immigration of sufficient numbers of eosinophils into inflammatory areas might be one cause of the reduction of the inflammatory edema found in a previous investigation under similar conditions.

Topics: Acid Phosphatase; Animals; Arylsulfatases; Blood Proteins; Bradykinin; Carrageenan; Cell Movement; Chemotactic Factors; Chemotactic Factors, Eosinophil; Disease Models, Animal; Eosinophil Granule Proteins; Eosinophilia; Eosinophils; Female; Guinea Pigs; Histamine; Inflammation; Isoenzymes; Male; Neutrophils; Peroxidase; Peroxidases; Platelet Activating Factor; Ribonucleases; Time Factors; Trichinellosis

The cellular biocompatibility of low-density polyethylene and a cytotoxic polyvinylchloride were investigated using an in vivo cage implant system. Components of the inflammatory response (white cells, extra-cellular alkaline and acid phosphatase, the complement component C3, and total protein content) were monitored over a 21-day implantation period. Scanning electron microscopy was used to evaluate the morphologic condition of leukocytes adherent to the implanted polymers. Prior to implantation, each polymer was evaluated using an established primary acute toxicity screen. The results showed that the cytotoxic polyvinylchloride stimulated an intense acute phase inflammatory response, and at later observation periods, an intense and increasing chronic inflammatory response. In contrast, the polyethylene promoted relatively small increases in the acute and chronic phases of inflammation; the overall cellular response being essentially resolved by the third week after implantation. The initial toxicity screen of each polymer suggested that the observed differences in inflammation were primarily caused by the release from the polyvinylchloride of the added cytotoxic agent (dioctyltinbisoctylmercaptoacetate).

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biocompatible Materials; Cell Adhesion; Cell Survival; Exudates and Transudates; Female; Humans; Immunodiffusion; In Vitro Techniques; Inflammation; Lymphocytes; Polyethylenes; Polyvinyl Chloride; Polyvinyls; Proteins; Rats; Rats, Inbred Strains; Time Factors

Besides other mediators like prostaglandins, kinins and histamine, oxygen radicals potentiate inflammations. Vitamin E as natural antioxidant could scavenge radicals produced during an inflammation and therefore reduce the inflammatory response. In experiments with male Wistar rats maintained on a diet deficient in or supplemented with vitamin E for 6 weeks the influence of the administration of DL-alpha-tocopherol on the inflammation of the right hind paw was tested. The irritation produced by injection of Freund's complete adjuvants was observed for 21 days. Measuring the thickness of the paw and the activity of acid phosphatase in the paw tissue there was no difference in the intensity of inflammation among the control and the vitamin-E-deficient diet groups. The supplementation with a pharmacological dose of tocopherol (324 mg DL-alpha-tocopherol/100 g food) had no effect on the inflammation of animals with different vitamin E supplements. Differences in the antioxidant status (contents of tocopherol and malondialdehyde in several organs, activity of creatine kinase in plasma) among the groups were mainly linked to the various tocopherol supplies. The irritation increased the lipid peroxidation in liver mitochondria and the activity of creatine kinase in the plasma. The data show no influence of vitamin E on this kind of inflammation.

Topics: Acid Phosphatase; Animals; Creatine Kinase; Free Radicals; Inflammation; Male; Malondialdehyde; Rats; Rats, Inbred Strains; Vitamin E

Topics: Acid Phosphatase; Administration, Topical; Alkaline Phosphatase; Animals; Bandages; Collagen; Female; Hydroxyproline; Inflammation; Rats; Wound Healing; Zinc; Zinc Oxide

The role of zinc in an occlusive, adhesive dressing (Zn-tape) was investigated in two experiments in the rat. In the first one Zn-tape was compared with a similar tape without zinc components and also with an inert plastic coated fabric with regard to the wound inflammatory reaction in excisional wounds. In the second experiment we attempted to assess possible systemic effects of zinc absorbed from Zn-tape-treated excisional wounds by studying the granulation tissue formation in subcutaneously implanted Ivalon sponges. The excisional wounds were treated with either the Zn-tape or a titanium tape in which the zinc oxide was replaced by an equivalent amount of titanium dioxide (Ti-tape). The granulation tissue produced was evaluated histologically, histochemically and biochemically. The plain adhesive mass and the Ti-tape elicited an intense inflammatory reaction as indicated both by high activities of alkaline phosphatases and histological examination. The Zn-tape reduced inflammatory processes in the granulation tissue of the excisional wounds. Zinc levels in serum and liver were raised in Zn-tape-treated animals. We conclude that zinc oxide in the Zn-tape affects inflammatory reactions in the granulation tissue of the wounds, possibly through a continuous release of zinc ions and by modifying the adhesive components of the Zn-tape. There was no evidence of a systemic effect of zinc absorbed from the excisional wounds on the granulation tissue formation in the implanted Ivalon sponges.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Collagen; Dermatologic Surgical Procedures; Female; Granulation Tissue; Inflammation; Occlusive Dressings; Rats; Rats, Inbred Strains; Wound Healing; Zinc; Zinc Oxide

6-Sulfanilamidoindazole (6-SAI) is a sulfonamide that induces inflammation in the ankles and hind paws of older rats and sensitizes the animals to the lethal actions of endotoxin. Sensitization is associated with reductions in plasma glucose concentration but not changes in phagocytic function of the RES or increases in lysosomal or hepatic enzymes. Death in 6-SAI-pretreated but not control rats was associated with fibrin deposition in the glomerular capillaries (generalized Shwartzman reaction) and inflamed paws. Endotoxin shock in both 6-SAI-pretreated and control rats was associated with increases in activities of lysosomal and hepatic enzymes and hypoglycemia. Methylprednisolone but not desoxycorticosterone pretreatment protected 6-SAI-fed rats against endotoxin lethality and the generalized Shwartzman reaction and maintained the plasma glucose concentration but did not prevent loss of lysosomal integrity. Simultaneous administrations of small doses of phenylbutazone with 6-SAI suppressed inflammation but did not protect against endotoxin lethality or the generalized Shwartzman reaction.

Topics: Acid Phosphatase; Alanine Transaminase; Animals; Blood Glucose; Desoxycorticosterone; Endotoxins; Glucuronidase; Hypoglycemia; Inflammation; Male; Methylprednisolone; Mononuclear Phagocyte System; Phagocytosis; Phenylbutazone; Rats; Rats, Inbred Strains; Shwartzman Phenomenon; Sulfanilamides

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adrenal Glands; Animals; Anti-Inflammatory Agents; Catechols; Cathepsin D; Curcumin; Female; Glucuronidase; Ibuprofen; Inflammation; Male; Prostaglandins; Rats; Stimulation, Chemical

A carcinoma invasion system (Krebs-2 and Ehrlich tetraploid ascites tumors invading mouse peritoneum) was studied by high-voltage electron microscope (HVEM) stereoscopy, conventional (medium voltage) electron microscopy (MVEM), and cytochemistry. Tumor cells entered areas of peritoneum (mainly parietal) only where mesothelial cells were damaged and where there was inflammation of the underlying stroma. The initial invasion was different from that of most other invading carcinomas in that there was minimal breakdown of basal lamina and collagen. Neither tumor cells, inflammatory leukocytes nor peritoneal fibroblasts showed significant secondary lysosome production or release of intracellular or extracellular acid phosphatase. Morphological and cytochemical criteria suggest that in some invading carcinomas, as with non-tumor migrating cells such as leukocytes, widespread proteolysis due to diffusion of proteases is not a prerequisite for invasion of stromal connective tissue.

Topics: Acid Phosphatase; Animals; Ascites; Basement Membrane; Carcinoma; Collagen; Extracellular Matrix; Inflammation; Lysosomes; Mice; Peptide Hydrolases; Peritoneal Neoplasms

A cage implant system has been utilized to examine the in vivo biocompatibility of a biodegradable hydrogel, poly(2-hydroxy-ethyl-L-glutamine) (PHEG). This system permits the quantitative determination of the components of the inflammatory exudate which surrounds the implanted polymer within the cage system. This system permits the serial examination of exudate components without sacrificing the animal. In addition, this system allows the subsequent removal of the polymer for surface and mechanical studies. Following implantation of the biodegradable hydrogel, quantitative and differential white cell counts of the exudates were determined over a 21-day period. In addition, concomitant extracellular enzyme analyses for alkaline phosphatase, acid phosphatase, prostatic acid phosphatase, leucine amino-peptidase, and Cathepsin B1 were determined. Corresponding control samples from exudates of the cage implant without the polymer were also determined. The two-tailed Student's t-test for unpaired samples was used to statistically compare the control and implanted polymer values for these respective analyses at the various time periods. A comparison of the cellular response for the control system and the PHEG system did not show statistically significant differences during the first 7 days following implantation. The acute inflammatory response, polymorphonuclear leukocyte predominant, was followed by a mild chronic inflammatory response, macrophage and lymphocyte predominant, and during this time period, 8-14 days, macrophages were present in significantly larger numbers for the PHEG system when compared to the control values. Enzymic analysis of the exudates revealed statistically significant differences between control and PHEG values at time intervals where no differences were noted in cell density or population. These results are discussed in terms of cell-polymer interactions leading to cellular activation and enhanced enzyme exocytosis by the inflammatory cells. Stress-strain measurements on implanted PHEG samples showed that significant in vivo degradation had occurred during the acute inflammatory phase of the response, i.e., the first 7 days.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biocompatible Materials; Biodegradation, Environmental; Blood Cell Count; Cell Adhesion; Chemotaxis; Extracellular Space; Exudates and Transudates; Inflammation; Neutrophils; Peptides; Prostheses and Implants; Proteins; Rats; Stainless Steel

Topics: Acid Phosphatase; Cathepsins; Glucosephosphate Dehydrogenase; Glycoproteins; Glycosaminoglycans; Humans; Inflammation; Rheumatic Fever; RNA

Enzyme activities in the circulating lymphocytes permit to judge the character of the regenerative process in the lung, and the severity of the patient's condition; it helps in estimating the prognosis and in evaluating the efficacy of the applied therapy. Potassium orotate and Riboxin intensify the regenerative process in the lung undergoing a compensatory-hypertrophic rearrangement, and enhance the functional activity of circulating lymphocytes as participants of the regenerative process and stimulate the oxidation-reduction processes in lymphocytes.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Glycerolphosphate Dehydrogenase; Humans; Hypertrophy; Inflammation; Inosine Diphosphate; L-Lactate Dehydrogenase; Lung; Lymphocyte Activation; Lymphocytes; Male; Neutrophils; Orotic Acid; Purines; Pyrimidines; Rats; Regeneration; Succinate Dehydrogenase; Uracil

Topics: Acid Phosphatase; Animals; Exocytosis; Glucuronidase; Inflammation; Leukocytes; Lysosomes; Rabbits

Activity of lysosomal hydrolases, cathepsins A and D, acid phosphatase, was induced in inflamed rat hypodermic tissue. Simultaneously, cytoplasmic enzymes leucine amino-peptidase and alkaline phosphatase were activated in the tissue. At the same time, activity of thiol-dependent enzymes/cathepsins B and C/ was decreased in all preparations studied. The data obtained suggest that both lysosomal and membrane-bound hydrolases participated in development of inflammation. Besides, proliferation of the hypodermic tissue appears to effect, by means of mediator and metabolite systems, on activity of intracellular enzymes in other tissues studied, which were not related directly to the impairment.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carboxypeptidases; Cathepsin A; Cathepsin B; Cathepsin D; Cathepsins; Inflammation; Leucyl Aminopeptidase; Phosphoric Monoester Hydrolases; Rats

A foreign body was introduced into the rabbit abdominal cavity. Macrophages, polymorphonuclear leukocytes (PMNL), lymphocytes of the abdomino-cavitary exudate, blood, trachea were examined cytochemically, whilst the tissue being formed around the foreign body and lungs were subjected to histological study. It was shown that three levels of structural and functional reconstitution of macrophages, PMNL and lymphocytes accompanied the development of aseptic inflammation. The system level determines the likeness of alterations of macrophages, PMNL and lymphocytes of different sites. The regional and cellular levels are responsible for the difference between the cells of different sites and types. A relationship was disclosed between the system reconstitution and the local (capsule) and distant (lung) tissue inflammation. The alterative and exudative tissue processes depend on the damage to macrophages, PMNL and lymphocytes. Meanwhile the proliferative processes depend on the changes in the biosynthesis of these cells.

Topics: Acid Phosphatase; Animals; Deoxyribonucleoproteins; Dihydrolipoamide Dehydrogenase; Inflammation; Lymphocytes; Macrophages; Neutrophils; Proteins; Rabbits; Ribonucleoproteins

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Colony-Forming Units Assay; Concanavalin A; Exudates and Transudates; Immunoglobulin G; Immunoglobulin M; Inflammation; Male; Mice; Mice, Inbred BALB C; Phagocytes; Phagocytosis; Propionibacterium acnes; Thioglycolates

Three experimental animal models have been used in the studies on the stimulatory effect of coumarin and levamisole. Both coumarin and levamisole increases cell coverage on subcutaneous implanted glass coverslip in mice. An increase in intracellular phosphatase activity was also observed. Stimulated mouse peritoneal cells when treated in vivo with coumarin or levamisole and then cultured in vitro showed increases acid phosphatase secretion (both extracellular and intracellular) as compared to control. Coumarin reduced the primary lesion of adjuvant-induced arthritis in rats. However, it potentiates the secondary lesions. Levamisole has no effect on the primary lesion but potentiates the secondary lesions. There was an increase in spleen and adrenal weights which correlate well with the severity of the secondary lesions. Increase in liver weight was only observed in coumarin-treated animals, an observation which suggests that coumarin may be a powerful mononuclear phagocytes system stimulant. The similarities and differences between coumarin and levamisole in their mode of action will be discussed.

Topics: Acid Phosphatase; Animals; Arthritis, Experimental; Coumarins; Glass; In Vitro Techniques; Inflammation; Levamisole; Macrophages; Male; Mice; Organ Size; Rats

Isopycnic sedimentation has been used to separate granulocytes of varying stages of maturity from the bone marrows of normal rabbits and rabbits stimulated to undergo an intense inflammatory response. The separated cell populations were in turn utilized to study the specific activities of six intracellular enzymes. The study revealed an increase with cell maturation in the specific activities of myeloperoxidase, NADPH oxidase, alkaline phosphatase and acid phosphatase in normal animals; in stimulated animals only myeloperoxidase and NADPH oxidase increased significantly with cell maturation. Glucose-6-phosphate dehydrogenase showed no change in specific activity in all animals studied. Malate dehydrogenase tended to show a specific activity decrease in the maturing cells of normal but not in those of stimulated animals.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Glucosephosphate Dehydrogenase; Granulocytes; Inflammation; Leukocyte Count; Leukocytes; Malate Dehydrogenase; NADH, NADPH Oxidoreductases; NADP; Peroxidase; Rabbits

The effect of altering endogenous leucocyte cyclic AMP levels on phagocytosis and lysosomal enzyme release was studied in vivo. Acute pleural exudates were produced in rats using either calcium pyrophosphate dihydrate crystals or rat serum. Despite marked increases in leucocyte cyclic AMP concentration produced by injection of dibutyryl cyclic AMP and theophylline, there was no reduction in crystal phagocytosis or in enzyme discharge.

Topics: Acid Phosphatase; Animals; Bucladesine; Cyclic AMP; Exudates and Transudates; Glucuronidase; Inflammation; L-Lactate Dehydrogenase; Leukocytes; Male; Phagocytosis; Pleurisy; Rats; Theophylline

In the wall of rat's capillary blood vessels the adenosine triphosphatase is located on the endothelium, the 5'nucleotidase on the perithelial cells. The perithelial cells activities are strong during the inflammatory state, but at the beginning of the phenomenon the nucleotidasic cells become free into the oedematous tissue by preceding and accompagning the fibroblastic differenciation cells.

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Capillaries; Inflammation; Male; Nucleotidases; Phosphoric Monoester Hydrolases; Rats; Skin; Time Factors

An inflammatory response was induced by the implantation of cover-slips into the brains of rabbits. The cytomorphology of the glass-adhering cells, their phagocytic properties and their enzymatic activity were characterized and these features were correlated with the presence of membrane markers. Mononuclear cells with foamy cytoplasm, with marked phagocytic potential and strong activity of nonspecific esterases consistently showed IgG- and C-receptor activity. Multinuclear giant cells, which increased in number after prolonged implantation, exhibited comparable features. In contrast, mononuclear cells of fusiform appearance with a low activity of nonspecific esterases and a poor phagocytic potential lacked the IgG-receptor. A close relationship between the mononuclear phagocytic cell and reactive microglia is postulated. The authors conclude that the inflammatory response observed under their test conditions was characterized by the prevalence of phagocytic cells with membrane characteristics of the monocyte-macrophage series.

Topics: Acid Phosphatase; Animals; Antigen-Antibody Reactions; Brain; Cell Membrane; Esterases; Inflammation; Neuroglia; Phagocytes; Rabbits; Time Factors; Wound Healing

Topics: Acid Phosphatase; Adolescent; Adult; Arylsulfatases; Cell Count; Child; Child, Preschool; Eosinophils; Female; Hodgkin Disease; Humans; Inflammation; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Spleen

An extract from Eisenia bicyclis, previously shown to possess anti-inflammatory activity, was found to stabilize lysosomal membranes in vitro as determined by measurement of inhibition of the marker enzyme beta-glucuronidase. Some anti-inflammatory activity was also due to counterirritancy.

Topics: Acid Phosphatase; Animals; Anti-Inflammatory Agents; Carrageenan; Eukaryota; Glucuronidase; In Vitro Techniques; Inflammation; Liver; Lysosomes; Male; Membranes; Plant Extracts; Rats

During the primary phase of inflammation of connective tissue of the paw there was an increase in enzyme activity among the resident connective tissue cells, probably as a result of catabolic processes (lytic processes, phagocytosis). As early as two days after the start of inflammation it was possible to recognize a close relationship between regeneration of the altered tissue (anabolic processes) and the increase of phosphomonoesterase activity in resident cells of the inflamed tissue. The role of the enzyme during inflammation was discussed.

Topics: Acid Phosphatase; Animals; Carrageenan; Fibroblasts; Foot; Granulocytes; Histiocytes; Histocytochemistry; Inflammation; Male; Rats

Topics: Acid Phosphatase; Animals; Aspirin; Capillary Permeability; Dactinomycin; Dose-Response Relationship, Drug; Edema; Evans Blue; Extremities; Glucuronidase; Histamine; Hydrocortisone; Indomethacin; Inflammation; Male; Rats

Topics: Acid Phosphatase; Alkaline Phosphatase; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Inflammation; Leukocytes; Neutrophils; Sepsis

To obtain direct evidence for the mechanism involved in gouty inflammation, human leukocytes were incubated with synthetic monosodium urate microcrystals. To trace the phago(lyso)somal contents, colloidal carbon, ferritin, Thorotrast(R) or horseradish peroxidase was added to the incubation medium, or acid phosphatase activity was localized cytochemically. The interaction was analyzed in time sequence by electron microscopy. By 5 minutes' incubation, urate crystals and tracers had appeared in the single membrane-bounded vacuoles of leukocytes. After 30 minutes' incubation, the vacuoles containing the urate crystals and the tracers were found in more than 50% of the leukocyte population. The phago(lyso)somal membrane was occasionally discontinuous, and the tracers were found in the free cytoplasm near the membrane opening as well. After 60 minutes' or more incubation, the phago(lyso)somal changes and the cytoplasmic localization of the tracers were common, and many cells showed signs of degeneration. Urate crystals mixed in cell debris were often found to be ingested by other leukocytes. These results have been interpreted as follows. Monosodium urate crystals are avidly phagocytized. The urate crystal-containing phagosomes eventually become phagolysosomes. The phagolysosomal membrane is damaged and the contents leak out into the cytoplasm. The leakage of the hydrolases initiates the host cell injury. The urate crystals released by cell disruption are again phagocytized by other cells and the series of events are repeated.

Topics: Acid Phosphatase; Animals; Carbon; Cell Membrane; Cell Separation; Colloids; Cytoplasm; Ferritins; Gout; Horses; Humans; Hydrolases; Inclusion Bodies; Inflammation; Leukocytes; Lysosomes; Microscopy, Electron; Peroxidases; Phagocytosis; Thorium Dioxide; Time Factors; Uric Acid

Topics: Acid Phosphatase; Animals; Autoradiography; Cell Fusion; Cell Nucleus; Cell Survival; Chromosomes; Colchicine; Histocytochemistry; Inflammation; Karyotyping; Macrophages; Male; Mice; Microscopy, Electron; Microscopy, Electron, Scanning; Mitosis; Phagocytosis; RNA; Succinate Dehydrogenase; Thymidine; Tritium; Uridine

Topics: Abnormalities, Drug-Induced; Acid Phosphatase; Animals; Cell Membrane; Drug Interactions; Drug Synergism; Edema; Embryo Implantation; Esters; Female; Fetal Death; Glucuronidase; Hindlimb; Inflammation; Lysosomes; Male; Methanol; Mice; Nicotinic Acids; Pregnancy; Rats; Salicylates; Stimulation, Chemical

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Cyclophosphamide; Dihydrolipoamide Dehydrogenase; Escherichia coli Infections; Glycerolphosphate Dehydrogenase; Guinea Pigs; Inflammation; Leukocyte Count; Lymphocytes; Neutrophils; Oxidoreductases; Phagocytosis; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Blood Vessels; Cicatrix; Dogs; Fibroblasts; Histocytochemistry; Inflammation; Peritoneum; Polyglycolic Acid; Postoperative Complications; Staining and Labeling; Sutures; Time Factors; Tissue Adhesions; Vascular Surgical Procedures; Vena Cava, Inferior

Topics: Acid Phosphatase; Chondrocalcinosis; Diphosphates; Female; Gout; Hemolysis; Humans; Inflammation; Leukocytes; Lysosomes; Male; Membranes; Phagocytosis; Sex Factors; Silicon Dioxide; Uric Acid

Topics: Acid Phosphatase; Adult; Brain Neoplasms; Central Nervous System Diseases; Cerebrospinal Fluid; Child, Preschool; Epilepsy; Female; Glioblastoma; Humans; Hypersensitivity; Inflammation; Lymphoma, Large B-Cell, Diffuse; Lysosomes; Male; Mental Disorders; Neurotic Disorders; Peptide Hydrolases; Psychotic Disorders; Vascular Diseases

Topics: Acid Phosphatase; Animals; Anti-Inflammatory Agents; Inflammation; Kaolin; Lysosomes; Membranes; Phenylbutazone; Pyrazines; Rats

Topics: Acid Phosphatase; Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Arthritis, Rheumatoid; Blood Sedimentation; Female; Hemoglobinometry; Histocytochemistry; Humans; Inflammation; Male; Middle Aged; Neutrophils; Nucleotidases; Osteoarthritis; Serum Albumin; Synovial Fluid; Synovial Membrane; Synovitis

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Fibroblasts; Guinea Pigs; Hair; Histocytochemistry; Inflammation; Necrosis; Nucleotidases; Radiation Effects; Radiation Injuries, Experimental; Regeneration; Sebaceous Glands; Skin; Time Factors; Ulcer

Topics: Acid Phosphatase; Carbon Isotopes; Culture Media; Dehydroepiandrosterone; Diethylstilbestrol; Estradiol; Female; Glucose; Humans; Inflammation; Leukocytes; Male; Methods; Oxygen Consumption; Phagocytosis; Pregnancy; Progesterone; Sex Factors; Staphylococcus

Topics: Acid Phosphatase; Animals; Antibody Formation; Chagas Disease; Female; Fluorescent Antibody Technique; Heart Atria; Inflammation; Lymphocytes; Lysosomes; Macrophages; Methods; Myocarditis; Myocardium; Phagocytosis; Pinocytosis; Rats; Rats, Inbred Strains; Trypanosoma cruzi

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Cortisone; Female; Glucocorticoids; Hexosaminidases; Humans; Hydrocortisone; Inflammation; Lysosomes; Male; Middle Aged; Prednisolone; Synovial Fluid; Synovial Membrane

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Anti-Inflammatory Agents; Aspirin; Betamethasone; Carrageenan; Dexamethasone; Edema; Female; Glucuronidase; Hexosaminidases; Indomethacin; Inflammation; Lysosomes; Methotrexate; Nystatin; Phenylbutazone; Prednisolone; Rats; Time Factors

Lysates of mixed human leukocyte suspensions released histamine from intact human leukocytes in vitro. Microgram quantities of leukocyte lysate protein released up to 90% of the total available histamine. The mixed leukocyte lysates were separated by differential centrifugation into nuclear (800 g pellet), lysosomal (25,000 g pellet), and postlysosomal supernatant (25,000 g supernatant) fractions. The degree of separation of the lysosomal from the other two fractions was assessed by measuring the relative activities of four lysosomal enzymes. The average distribution of enzyme activity was 11 +/-2% (mean +/-1 SD), 72 +/-10%, and 17 +/-8% for the nuclear, lysosomal, and supernatant fractions respectively. The histamine-releasing activity was equally distributed between the lysosomal and supernatant fractions, each of which had 5-fold greater activity than the nuclear fraction. Purified suspensions of platelets, lymphocytes, and granulocytes were prepared, and the lysates of these suspensions all had histamine-releasing activity. Centrifugation at 100,000 g for 18 hr sedimented the histamine-releasing activity from all three types of lysate. After 20% ethanol fractionation for the preparation of cationic protein, only the activity from the platelet lysates was found in the 20% ethanol insoluble fraction. These mediators of histamine release from human platelets, lymphocytes, and granulocytes may play a role in the development of the vasodilation and increased vascular permeability which characterize the acute inflammatory response.

Topics: Acid Phosphatase; Blood Platelets; Capillary Permeability; Cathepsins; Glucuronidase; Histamine Release; Humans; In Vitro Techniques; Inflammation; Leukocytes; Lymphocytes; Lysosomes

1. Autografts and homografts of full thickness skin were made on a hind limb of rabbits. During the following days the appearance and histological changes of the grafts were studied; the lymph flow from the limb, and the enzyme activities in the supernatant and cell pellet of the lymph after centrifugation were determined, as well as the enzyme activities in the graft roof and the underlying host tissue. It was further examined whether a lymphatic and vascular connexion occurred between graft and host tissue.2. During the first 5 days the grafts changed from pale blue to bright pink, became swollen, soft and had a mild cellular inflammatory exudate. Autografts then became pale, took on the appearance of normal skin with the inflammatory changes subsiding, whereas homografts became firm, showed heavy mononuclear cell infiltration, had a blotchy purple appearance due to thrombosis and haemorrhage, developed widespread necrosis and changed into a black hard scab which was eventually shed. With high dose homografts (6-8 grafts) these changes occurred 1-2 days earlier than with low dose (2-4) grafts.3. The flow of lymph increased during the first 5 days after grafting, then returned to normal with autografts but remained increased with homografts.4. In the supernatant of the lymph the activities of LDH and beta-glucuronidase did not change during the first 5 days but activities of cathepsin, acid phosphatase, GOT and GPT increased. With the autografts the increase in the activities of these four enzymes then subsided, but with the homografts they increased further and there was an increase in the activities of LDH and beta-glucuronidase, even greater than in those of the other four enzymes.5. In the cell pellets of the lymph the activities of the six enzymes did not increase during the first 5 days; with homografts, but not with autografts, they then increased. These increases occurred even though the cell count in the pellet remained unchanged. Thus some of the lymphocytes must have become ;activated' to contain higher enzyme activities.6. The enzyme activities in the roof tissue did not parallel those in lymph. They did not change during the first three days. During the following three days the activities of acid phosphatase, LDH, beta-glucuronidase and cathepsin increased, but not those of GOT and GPT which remained low. From then onwards the behaviour was different with auto- and homografts. With autografts only the activity of acid phosphatase continued t

Topics: Acid Phosphatase; Alanine Transaminase; Animals; Aspartate Aminotransferases; Cathepsins; Glucuronidase; Graft Rejection; Hemorrhage; Hindlimb; Inflammation; L-Lactate Dehydrogenase; Lymph; Lymphocytes; Necrosis; Rabbits; Skin; Skin Transplantation; Thrombosis; Time Factors; Transplantation, Autologous; Transplantation, Homologous; Wound Healing

Topics: Acid Phosphatase; Adult; Arthritis, Infectious; Arthritis, Rheumatoid; Blood Cell Count; Electrophoresis; Humans; Inflammation; Isoenzymes; Leukocyte Count; Lymphocytes; Osteoarthritis; Synovial Fluid; Synovitis

Topics: Acid Phosphatase; Adult; Bites and Stings; Dermatitis; Female; Glucosephosphate Dehydrogenase; Humans; Inflammation; L-Lactate Dehydrogenase; Neurodermatitis; Prurigo; Skin; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adipose Tissue; Alkaline Phosphatase; Aminohydrolases; Animals; Blister; Epithelium; Fibroblasts; Forensic Medicine; Frostbite; Guinea Pigs; Histocytochemistry; Inflammation; L-Lactate Dehydrogenase; Oxidoreductases; Skin; Time Factors

Topics: Acid Phosphatase; Acute Disease; Alkaline Phosphatase; Alpha-Globulins; Animals; Beta-Globulins; Calcium; Chlorides; Chronic Disease; Exudates and Transudates; gamma-Globulins; Inflammation; Mucoproteins; Phospholipids; Phosphorus; Potassium; Rabbits; Serum Albumin; Serum Globulins; Sodium

Topics: Acid Phosphatase; Acute Disease; Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Exudates and Transudates; Female; Fructose-Bisphosphate Aldolase; Inflammation; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Malate Dehydrogenase; Male; Rabbits

Topics: Acid Phosphatase; Animals; Ceruloplasmin; Female; Fibrinogen; Glucuronidase; Hydrolases; Inflammation; Lysosomes; Mucoproteins; Radiation Injuries, Experimental; Rats; Sulfatases

Topics: Acid Phosphatase; Analgesics; Animals; Anti-Inflammatory Agents; Antibody Formation; Aspirin; Blood Platelets; Blood Proteins; Cell Aggregation; Cyclophosphamide; Depression, Chemical; Fibrinolysis; Flufenamic Acid; Glucuronidase; Guinea Pigs; Hemolysis; Hydrocortisone; Indomethacin; Inflammation; Male; Mefenamic Acid; Mice; Phenylbutazone; Protein Binding; Protein Denaturation; Pyridines; Rabbits; Rats; Stimulation, Chemical

Topics: Acid Phosphatase; Adenosine Triphosphate; Alkaline Phosphatase; Aminopeptidases; Connective Tissue; Endometrium; Epithelium; Esterases; Female; Glucosephosphate Dehydrogenase; Glutamate Dehydrogenase; Glycerolphosphate Dehydrogenase; Histocytochemistry; Humans; Hydroxybutyrate Dehydrogenase; Inflammation; Isocitrate Dehydrogenase; L-Lactate Dehydrogenase; Malate Dehydrogenase; NAD; NADP; Neoplasm Metastasis; Oxidoreductases; Phosphoric Monoester Hydrolases; Uterine Neoplasms

Topics: Acid Phosphatase; Female; Histocytochemistry; Humans; Inflammation; Macrophages; Male; N-Glycosyl Hydrolases; Skin Window Technique; Succinate Dehydrogenase

Topics: Acid Phosphatase; Blood Cells; Cell Differentiation; Culture Techniques; Esterases; Inflammation; Macrophages; Monocytes; Peroxidases; Skin Window Technique

Topics: Acid Phosphatase; Animals; Disease Models, Animal; Eye Diseases; Inclusion Bodies, Viral; Inflammation; Lacrimal Apparatus; Lysosomes; Microscopy, Electron; Parotid Gland; Rats; Rodent Diseases; Salivary Gland Diseases; Submandibular Gland; Virus Diseases

Topics: Acid Phosphatase; Acute Disease; Aminocaproates; Animals; Arthritis; Cartilage, Articular; Chronic Disease; Glucuronidase; Hot Temperature; Hydrolases; Hypertrophy; Inflammation; Injections, Intra-Articular; Leukocytes; Lysosomes; Peptide Hydrolases; Rabbits; Skin; Synovial Membrane

Topics: Acid Phosphatase; Animals; Estrus; Female; Glucuronidase; Glycogen; Inflammation; Intrauterine Devices; Leukocytes; Lysosomes; Pregnancy; Rats; Serum Albumin, Bovine; Uterus

Topics: Acid Phosphatase; Animals; Antigens; Glucuronidase; Immune Sera; Immunoglobulin G; Inflammation; Isocitrate Dehydrogenase; Liver; Lysosomes; Membranes; Mitochondria; Rabbits; Rats

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Cell Biology; Cell Movement; Chemotaxis; Culture Techniques; Glucuronidase; Inflammation; Leukocytes; Lysosomes; Macrophages; Muramidase; Neutrophils; Rabbits

Topics: Acid Phosphatase; Anaphylaxis; Animals; Antibody Formation; Antigen-Antibody Reactions; Arthus Reaction; Blood Cell Count; Blood Platelets; Blood Pressure; Fluorescent Antibody Technique; Glucuronidase; Hemorrhage; Hydrolases; Hypersensitivity; Hypotension; Immunity, Active; Immunity, Maternally-Acquired; Inflammation; Injections, Intravenous; Leukocytes; Leukopenia; Lung; Lysosomes; Methods; Microscopy, Electron; Microscopy, Fluorescence; Peptide Hydrolases; Pulmonary Circulation; Rabbits; Rats; Serum Albumin, Bovine; Swine

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Dihydrolipoamide Dehydrogenase; Dumping Syndrome; Duodenum; Esterases; Gastrectomy; Glycosaminoglycans; Histocytochemistry; Humans; Inflammation; Intestinal Mucosa; Intestine, Small; Leucyl Aminopeptidase; Methods; Middle Aged; Oxidoreductases; RNA; Succinate Dehydrogenase

Topics: Acid Phosphatase; Aminocaproates; Animals; Antifibrinolytic Agents; Aprotinin; Carbon Tetrachloride Poisoning; Chymotrypsin; Cyclohexanecarboxylic Acids; Edema; Female; Fibrinolysin; Guinea Pigs; Inflammation; Kallikreins; Microbial Collagenase; Pancreatic Elastase; Peptides; Protease Inhibitors; Rats; Ribonucleases; Trypsin

Topics: Acid Phosphatase; Animals; Arthritis; Centrifugation, Density Gradient; Coliphages; Electron Transport Complex IV; Glucuronidase; Hydrolases; Inflammation; Joints; Liver; Lysosomes; Malate Dehydrogenase; Male; Mitochondria, Liver; Rabbits; Sulfatases; Thorium Dioxide

Topics: Acid Phosphatase; Animals; Exudates and Transudates; Female; Glucuronidase; Inflammation; Leukocytes; Lysosomes; Male; Mercaptopurine; Methods; Rabbits; Ribonucleases

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Autoradiography; DNA; Estrus; Female; Histocytochemistry; Inflammation; Neutrophils; Pregnancy; Pregnancy, Animal; Rats; Succinate Dehydrogenase; Thymidine; Uterus

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Dihydrolipoamide Dehydrogenase; Esterases; Histiocytes; Inflammation; L-Lactate Dehydrogenase; Macrophages; Mast Cells; Oxidoreductases; Phosphoric Monoester Hydrolases; Rats; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Esterases; Humans; Inflammation; Lysosomes; Monocytes; Peptide Hydrolases; Skin Window Technique

Topics: Acid Phosphatase; Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Blood Glucose; Blood Proteins; Female; Fructose-Bisphosphate Aldolase; Hematocrit; Hemoglobinometry; Horse Diseases; Horses; Hyaluronoglucosaminidase; Hydrarthrosis; Hydroxyprogesterones; Hydroxysteroid Dehydrogenases; Inflammation; L-Lactate Dehydrogenase; Male; Synovial Fluid; Tarsal Joints

Topics: Acid Phosphatase; Adipose Tissue; Alkaline Phosphatase; Aminopeptidases; Animals; Guinea Pigs; Histocytochemistry; Inflammation; Lymphoid Tissue; Macrophages; Muscles; Pathology; Physiology; Skin; Tuberculin; Tuberculin Test; Veins

Topics: Acid Phosphatase; Basophils; Blood Platelets; Connective Tissue Cells; Electrons; Endothelial Cells; Eosinophils; Erythrocytes; Histocytochemistry; Inflammation; Leukocyte Count; Leukocytes; Lymphocytes; Mesentery; Microscopy; Microscopy, Electron; Monocytes; Rats; Research

Lysosomal granules of rabbit exudate polymorphonuclear (PMN) leucocytes were isolated and then lysed by freezing-thawing. Topical application of this material to rat and rabbit mesentery produced sticking and emigration of leucocytes, stasis of blood flow, and petechial hemorrhage. The granule-free, supernatant fraction of the homogenized leucocytes failed to produce any of these reactions. Cationic proteins extracted from these granules by weak acid and precipitated by ethanol at concentrations of 20 and 45 per cent, were also tested on heterologous, homologous, and autologous mesenteric vessels. The 20 per cent ethanol-precipitated fraction produced all of the aforementioned injury reactions, whereas the 45 per cent fraction was inactive. The intensity of inflammatory changes produced by the active cationic protein fraction was greater than that produced by lysed whole granules. Both the 20 per cent and 45 per cent ethanol fractions of cationic protein induced clumping of rabbit platelets, in vitro. The 20 per cent ethanol fraction also caused a slight acceleration in rate of swelling of isolated rabbit liver mitochondria. The active material proved to be non-pyrogenic in rabbits. This material exhibited no kinin-like effects when tested on isolated smooth muscle preparations (rabbit aorta and guinea pig ileum). In the rat, the protein produced a transient vasodepression which was inhibited by pretreatment of the animal with an antihistamine. Ultraviolet absorption data and ribose assays showed that the 20 per cent ethanol fraction contained only 4 per cent or less of ribonucleic acid. Upon electrophoresis in starch gel, using acid buffer, this fraction separated into at least three major components which migrated towards the cathode. Precipitation of one of the slowly migrating components by titration of the fraction to pH 10.5 greatly increased the inflammatory activity of the material. The inflammatory basic protein fraction was essentially devoid of acid phosphatase, beta glucuronidase, acid ribonuclease, lysozyme, and catalase activity. The non-inflammatory basic protein fraction contained appreciable quantities of acid ribonuclease and lysozyme. The foregoing data demonstrate that certain of the cationic proteins present in lysosomes of rabbit exudate PMN leucocytes can reproduce one of the cardinal features of the inflammatory response; namely, adhesion and emigration of leucocytes in the microcirculation. These findings offer fresh support for t

Topics: Acid Phosphatase; Animals; Bradykinin; Capillary Permeability; Cytoplasmic Granules; Exudates and Transudates; Glucuronidase; Guinea Pigs; Histamine; Inflammation; Leukocytes; Lysosomes; Mesentery; Microcirculation; Mitochondria; Muramidase; Muscle, Smooth; Neutrophils; Norepinephrine; Pharmacology; Promethazine; Proteins; Rabbits; Rats; Research; Ribonucleases; RNA; Toxicology

Topics: Acid Phosphatase; Alkaline Phosphatase; Electron Transport Complex II; Granuloma; Histocytochemistry; Inflammation; Liver; Lymph Nodes; Mononuclear Phagocyte System; Rats; Research; Spleen; Succinate Dehydrogenase