acid-phosphatase and Sarcoidosis

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

Cathepsin K and tartrate-resistant acid phosphatase (TRAP) are two proteins expressed in osteoclastic giant cells. Recently we showed that lesional multinucleated giant cells (MNGs) in pulmonary granulomatosis with polyangiitis expressed these proteins. We aimed to clarify whether the expression of these two proteins has any specificity or is a general feature of MNGs associated with multiple types of granulomatous inflammation.. In total, 7 Crohn's disease (CD), 5 GCA, 5 giant cell myocarditis (GCM), 11 sarcoidosis and 6 tuberculosis cases were examined for expression of cathepsin K and TRAP using immunohistochemistry (IHC). Protein expression was semi-quantitatively classified as none, weak, moderate or strong. In addition, tissue TRAP activity was examined using an enzymatic reaction.. The expression of cathepsin K was robust in >95% of MNGs of all examined disease groups, whereas TRAP expression varied; CD, GCA and tuberculosis showed strong TRAP expression. TRAP expression in sarcoidosis and GCM was weaker (CD vs GCM, P = 0.04; CD vs sarcoidosis, P = 0.06). Compared with IHC, TRAP detection using an enzymatic colour reaction had limited sensitivity.. Expression of TRAP and cathepsin K is a general feature of MNGs and their expression might be related to histopathological pattern.

Topics: Acid Phosphatase; Biomarkers; Cathepsin K; Cells, Cultured; Crohn Disease; Giant Cells; Humans; Immunohistochemistry; Isoenzymes; Myocarditis; Osteoclasts; Paraffin Embedding; Sarcoidosis; Sensitivity and Specificity; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; Tuberculosis

In the present study about 0.3% to 1.6% of human bronchoalveolar lavage (BAL) cells were identified as typical dendritic cells (DC), having an irregular outline, lobulated nucleus, and clear distinguishable acid phosphatase activity or EBM11 (anti-CD68) reactivity in a spot near the nucleus. After DC enrichment, using transient adherence to plastic, FcR-panning, and a density metrizamide gradient, a population containing 7-8% typical DC was obtained. This DC-enriched low density fraction, containing the highest percentages of DC, very strongly induced T cell proliferation in an allogeneic mixed leucocyte reaction (MLR), which was significantly higher than that induced by other partly (un)fractionated BAL cells. These data indicate that DC seem to be the major accessory cells in the BAL fluid, and therefore may be important in the regulation of T cell immune responses in the lung.

Topics: Acid Phosphatase; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bronchoalveolar Lavage Fluid; Cell Separation; Dendritic Cells; Humans; Male; Middle Aged; Sarcoidosis

Tartrate-resistant acid phosphatase (TrACP) is abundant in alveolar macrophages, suggesting that these cells might contribute to the activity of this isoenzyme in sera of patients with conditions characterized by activation of alveolar macrophages. TrACP was therefore measured in patients with pulmonary sarcoidosis and cryptogenic fibrosing alveolitis and compared with values in controls. Since osteoclasts are known to be the main source of TrACP in serum several indices of bone-turnover were also measured: serum bone-specific alkaline phosphatase and urine hydroxyproline:creatinine ratios. Patients with Paget's disease of bone constituted a reference group presenting increased bone turnover. TrACP was not significantly higher in the lung-disease groups than in controls, although there was a strong positive correlation with angiotensin-converting enzyme in pulmonary sarcoidosis. As expected, TrACP activity was elevated together with the other indices of bone turnover in Paget's disease. It is unlikely that TrACP from alveolar macrophages contributes significantly to serum acid phosphatase activity in lung disease.

Topics: Acid Phosphatase; Adult; Aged; Female; Humans; Isoenzymes; Lung Diseases; Macrophage Activation; Male; Middle Aged; Osteitis Deformans; Pulmonary Fibrosis; Sarcoidosis; Tartrate-Resistant Acid Phosphatase; Tartrates

Five main acid phosphatase (AcP) zones have been recognized and studied by polyacrylamide-gel electrophoresis. Band 5 represents the only tartrate-resistant form and is present in bone osteoclasts and in human alveolar macrophages (AMs). This study was carried out to quantify the presence of total and tartrate-resistant AcP (TrAcP) in AMs from bronchoalveolar lavage (BAL) of 11 patients with first stage sarcoidosis and in 13 nonsmokers and 16 smokers serving as control healthy subjects. The AMs from smokers showed an increase in total AcP activity (115.9 +/- 77.8 mU/10(6)); on the contrary, macrophages of patients with sarcoidosis revealed a consistent decrease in total AcP (27.8 +/- 7.0 mU/10(6)) and particularly the TrAcP subtype (14.8 +/- 3.7 mU/10(6)) in comparison with control nonsmokers (AcP = 42.2 +/- 18.9 mU/10(6) [p = NS]; TrAcP = 35.1 +/- 15.1 mU/10(6) [p less than 0.005]). The decrease in TrAcP activity was inversely correlated with the lymphocyte number (r = -0.75; p less than 0.01), lymphocyte percentage (r = -0.62; p less than 0.05), and CD4/CD8 ratio (r = -0.61; p less than 0.05). After six months of follow-up, the cytologic BAL picture returned completely to normal in five patients with full spontaneous regression of sarcoidosis; and also at the same time, normal values of TrAcP activity were restored. Since TrAcP activity can be easily detected, its possible use, along with the lymphocyte count and CD4/CD8 ratio, as a prognostic indicator of the clinical course of sarcoidosis deserves further investigation.

Topics: Acid Phosphatase; Adult; Bronchoalveolar Lavage Fluid; CD4-Positive T-Lymphocytes; Female; Histocytochemistry; Humans; Leukocyte Count; Lung Diseases; Macrophages; Male; Pulmonary Alveoli; Regression Analysis; Sarcoidosis; Smoking; T-Lymphocytes, Regulatory; Tartrates

Topics: Acid Phosphatase; Acquired Immunodeficiency Syndrome; Humans; Lung Neoplasms; Macrophages; Phagocytosis; Pulmonary Alveoli; Sarcoidosis; Staphylococcus aureus

Alveolar macrophages differ from their percursors in blood, monocytes, by expressing strong activity of the tartrate resistant variant of acid phosphatase (TAcP). A study was carried out to analyse the expression of this enzyme cytochemical marker by alveolar macrophages from bronchoalveolar lavage cells from 34 patients with sarcoidosis and 12 control subjects. Alveolar macrophages from control subjects displayed a strong and homogeneous staining pattern and only 0.1% of cells were negative after staining. Macrophages from patients with sarcoidosis showed reduced TAcP activity and up to 7% of the cells were negative. The percentage of TAcP negative macrophages was correlated with the percentage of lymphocytes and with the ratio of CD4 to CD8 lymphocytes among cells recovered by bronchoalveolar lavage. The reduced TAcP activity in alveolar macrophages from patients with sarcoidosis may be due to an increased recruitment of immature precursors from blood.

Topics: Acid Phosphatase; Adult; Humans; Lung Diseases; Macrophages; Pulmonary Alveoli; Sarcoidosis; Tartrates

The development of skin-window macrophages was studied in four untreated patients suffering from sarcoidosis by cytochemical assessment of the acid phosphatase activity. The results obtained in these patients were compared with those of healthy volunteers. Appearance of the focal acid phosphatase-activity in the Golgi area was delayed in patients with sarcoidosis. A decreased amount of activity in mature macrophages was also demonstrated depending on the clinical activity of the disease. Patients with hypothyroidism showed the same cytochemical pattern. In contrast to these results, no significant difference in the development of acid phosphatase activity was found in patients with tuberculosis as compared to healthy volunteers. Our observations confirm the hypothesis that the functional disorder of monocytes is, at least, a partial pathogenetic mechanism of sarcoidosis.

Topics: Acid Phosphatase; Humans; Macrophages; Prognosis; Sarcoidosis; Skin Window Technique

Topics: Acid Phosphatase; Adolescent; Adult; Chronic Disease; Female; Histocytochemistry; Humans; Immunity, Cellular; Male; Middle Aged; Naphthol AS D Esterase; Recurrence; Respiratory Tract Diseases; Sarcoidosis; T-Lymphocytes

Cytospin preparations of mononuclear inflammatory cells were made from bronchoalveolar lavage fluid obtained from 15 patients with interstitial lung disease (nine patients with sarcoidosis and six patients with cryptogenic fibrosing alveolitis) and six control subjects. These preparations were examined with a panel of monoclonal antibodies that have been shown to distinguish subpopulations of macrophage like cells in normal tissues. The lysosomal acid phosphatase activity of the cells was also assessed. Phenotypically distinct subpopulations of alveolar macrophages were identified in all samples studied. The results showed that all cell populations identified in bronchoalveolar lavage fluid from the groups with interstitial lung disease could be identified in the lavage fluid from normal volunteers. Some quantitative differences in the proportions of cells identified with particular reagents emerged. In each of the groups with interstitial lung disease increased proportions of cells were identified with RFD1 (interdigitating cell marker; p less than 0.01) and in the cryptogenic fibrosing alveolitis group an increased proportion of alveolar macrophages was identified with RFD7 (tissue macrophage marker; p less than 0.05). The possibility that quantitative changes in alveolar macrophage subsets observed in the interstitial lung disease groups are relevant to the pathogenesis of these conditions is discussed.

Topics: Acid Phosphatase; Adult; Aged; Female; HLA-DR Antigens; Humans; Lung Diseases; Macrophages; Male; Middle Aged; Phenotype; Pulmonary Alveoli; Pulmonary Fibrosis; Sarcoidosis

Human alveolar macrophages (AM) were obtained by bronchoalveolar lavage from 18 patients with a variety of conditions. For each patient the percentages of AM showing the following properties were determined: (1) staining for the enzymes non-specific esterase (NSE) and acid phosphatase (ACP); (2) in vitro phagocytosis of Candida guillermondii; (3) expression of cell surface markers detected by two monoclonal antibodies (MoAb) (1B5 and DA2) and two anti-monocyte/macrophage MoAb (UCHMI and RFD2); and (4) simultaneous phagocytosis of C. guillermondii and staining with the MoAb. In all patients the majority of AM were found to be Ia positive (90 +/- 10%) ACP positive (100%) and NSE positive (97 +/- 4%). In contrast a smaller proportion were UCHM1 and RFD2 positive (77 +/- 11%, 68 +/- 12%) and less were phagocytic (37 +/- 17%). Whilst the total percentage of cells staining with the MoAb was unaltered by phagocytosis, the proportion of UCHM1 or RFD2 positive cells was significantly higher in the phagocytic population than in the non-phagocytic population (90% and 85%, as opposed to 65% and 55%, P less than 0.001). Thus only a proportion of Ia positive AM expressed monocyte/macrophage antigens and were phagocytic. Such heterogeneity may reflect different stages of macrophage maturation or the existence of macrophage subpopulations with functionally distinct roles in airways immunity.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Antigens, Surface; Carboxylesterase; Carboxylic Ester Hydrolases; Cell Count; Histocompatibility Antigens Class II; Humans; Lung Diseases; Lung Neoplasms; Macrophages; Phagocytosis; Pulmonary Alveoli; Sarcoidosis

Cytological, cytochemical and immunopathological investigations were carried out at lung washings in a case of pulmonary alveolar proteinosis. There was an increased activity of alveolar epithelial cells of type II (AEZ II) with increased production of surfactant lipids. Abundant lipids of the surfactant system are also visible in the extracellular material rich in protein and lipids. Alveolar macrophages showed increased enzymatic activity with high levels of acid phosphatase and nonspecific esterase, but no phagocytosis of surfactant lipids. Immunopathological investigations exhibit a high content of IgG, IgM and IgA in the exudate. These findings demonstrate, that exudation of blood serum in alveoli and overproduction of surfactant material are two important processes in the formal genesis of alveolar proteinosis, dependent on each other.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Epithelium; Esterases; Female; Fluorescent Antibody Technique; Humans; Immunoglobulins; Macrophages; Pulmonary Alveolar Proteinosis; Pulmonary Alveoli; Pulmonary Surfactants; Sarcoidosis

Topics: Acid Phosphatase; Histocytochemistry; Humans; Leukocytes; Lung Diseases; RNA; Sarcoidosis

Skin lesions from four patients with systemic and cutaneous sarcoidosis were studied, by the use of monoclonal antibodies, for the presence of T cells and T-cell subsets. Large numbers of lymphoid cells reacting with anti-pan T-cell (LEU-1) and anti-helper and inducer subset (LEU-3) monoclonal antibodies were observed around and within the sarcoid granulomas in three of the four patients. Only rare LEU-2-reactive suppressor cells were observed in all four patients. Activated T lymphocytes with focal acid phosphatase activity, together with epithelioid cells and multinucleated giant cells with strong diffuse activity of acid phosphatase and nonspecific esterase, were identified within the granulomas. The two patients with active disease demonstrated substantially more T cells in the sarcoid granulomas than did the two patients with chronic disease. Our study results suggest the importance of helper T cells in the formation of the sarcoid granuloma by mononuclear phagocytes and imply that the activity and duration of disease may be related to the T-cell populations.

Topics: Acid Phosphatase; Adult; Antibodies, Monoclonal; Carboxylesterase; Carboxylic Ester Hydrolases; Female; Humans; Immunoenzyme Techniques; Lymphocyte Activation; Male; Middle Aged; Sarcoidosis; Skin Diseases; T-Lymphocytes; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

The activities of tissue angiotensin-converting enzyme (ACE) were investigated in several skin diseases. Biopsy specimens were taken from 49 patients with granulomatous lesions, including sarcoidosis, 16 patients with nongranulomatous lesions, and 13 normal individuals. The ACE level was measured fluorometrically and the lysosomal enzyme levels were measured by established techniques. It was found that ACE activity increased in all granulomatous skin lesions, but not in other inflammatory lesions. The enzyme activity showed an increase that paralleled the time course of the disease. In contrast, lysosomal enzymes increased in various types of skin lesions, suggesting that they reflect nonspecific inflammation. These findings indicate that the tissue ACE level may be a marker for granulomatous inflammation, but one that is not specific for sarcoidosis.

Topics: Acid Phosphatase; Cathepsin D; Cathepsins; Galactosidases; Glucuronidase; Granuloma; Humans; Lysosomes; Peptidyl-Dipeptidase A; Sarcoidosis; Skin Diseases

Topics: Acid Phosphatase; Histocytochemistry; Humans; Leucyl Aminopeptidase; Lung; Lung Diseases; Lymph Nodes; Prognosis; Sarcoidosis

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Female; Glucuronidase; Humans; Lymphocytes; Male; Middle Aged; Sarcoidosis

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Enzyme Activation; Female; Glycogen; Histocytochemistry; Humans; Leukocytes; Lung Diseases; Male; Middle Aged; Peroxidase; Sarcoidosis

Topics: Acid Phosphatase; Alkaline Phosphatase; Antitubercular Agents; Clinical Enzyme Tests; Drug Therapy, Combination; Humans; Leukocytes; Lung Diseases; Prednisolone; Prognosis; Sarcoidosis; Vitamins

Topics: Acid Phosphatase; Asthma; Histocytochemistry; Humans; Lung Diseases; Lung Neoplasms; Neutrophils; Sarcoidosis

Topics: Acid Phosphatase; Adult; Female; Gaucher Disease; Humans; Male; Peptidyl-Dipeptidase A; Sarcoidosis

Parotid saliva from a patient suffering from sarcoidosis with salivary gland involvement has been shown to have a decreased level of alpha-amylase but increased levels of albumin and lysozyme. These observations suggest that in addition to impaired gland function, gland damage as a result of inflammation had occurred which permitted increased passage of constituents from serum into the gland secretion.

Topics: Acid Phosphatase; Albumins; Amylases; Muramidase; Parotid Gland; Peptide Hydrolases; Proteins; Ribonucleases; Saliva; Salivary Gland Diseases; Sarcoidosis

Topics: Acid Phosphatase; Epithelial Cells; Epithelium; Glycoproteins; Histocytochemistry; Humans; Lymph Nodes; Lymphokines; Macrophages; Microscopy, Electron; Sarcoidosis; Spleen

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Esterases; Glutamate Dehydrogenase; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Lymph Nodes; Malate Dehydrogenase; Mediastinum; Nucleotidases; Sarcoidosis; Staining and Labeling

Topics: Acid Phosphatase; Collagen; Humans; L-Lactate Dehydrogenase; Microbial Collagenase; Prednisolone; Sarcoidosis

Topics: Acid Phosphatase; Clinical Enzyme Tests; Collagen; Evaluation Studies as Topic; Follow-Up Studies; Humans; L-Lactate Dehydrogenase; Peptide Hydrolases; Sarcoidosis; Triamcinolone Acetonide

Topics: Acid Phosphatase; Acute Disease; Alkaline Phosphatase; Carcinoma; Chronic Disease; Electrophoresis; Hot Temperature; Humans; Lymph Nodes; Mediastinal Neoplasms; Mediastinum; Sarcoidosis

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Animals; Antibody Formation; Antigens; Cholelithiasis; Female; Glucuronidase; Hexosaminidases; Histocytochemistry; Humans; Lupus Erythematosus, Systemic; Lymph Nodes; Lymphocytes; Male; Peroxidases; Plasma Cells; Rabbits; Rats; Sarcoidosis; Stomach Neoplasms; Stomach Ulcer; Tuberculosis

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigen-Antibody Reactions; Biopsy; Epithelial Cells; Esterases; Granuloma; Histiocytes; Humans; Hypersensitivity, Delayed; Leukocytes; Lymphocytes; Lysosomes; Macrophages; Microscopy, Electron; Phagocytosis; Sarcoidosis; Skin Tests; Time Factors

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Marrow Examination; Female; Humans; Leukemia, Myeloid; Leukocyte Count; Leukocytes; Male; Muramidase; Nitrophenols; Remission, Spontaneous; Sarcoidosis

Topics: Acid Phosphatase; Epithelial Cells; Granuloma; Histocytochemistry; Humans; Microscopy, Electron; Mucoproteins; Sarcoidosis

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lymphoma; Male; Middle Aged; Multiple Myeloma; Muramidase; Sarcoidosis; Seasons

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Blood Proteins; Culture Techniques; Female; Glucuronidase; Hodgkin Disease; Humans; Infectious Mononucleosis; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Lymphoma, Follicular; Lysosomes; Malate Dehydrogenase; Male; Middle Aged; Plasmacytoma; Sarcoidosis; Waldenstrom Macroglobulinemia

Topics: Acid Phosphatase; Adult; Female; Glucuronidase; Granuloma; Histocytochemistry; Humans; Lymph Nodes; Male; Microscopy, Electron; Sarcoidosis

Topics: Acid Phosphatase; Diagnosis, Differential; Esterases; Granuloma; Humans; Lymph Nodes; Lysosomes; Prednisone; Sarcoidosis; Tuberculosis

Topics: Acid Phosphatase; Histocytochemistry; Humans; Lipids; Phospholipids; Proteins; Sarcoidosis