muramidase and Arthritis

Maintenance of healthy bone requires the balanced activities of osteoclasts (OCs), which resorb bone, and osteoblasts, which build bone. Disproportionate action of OCs is responsible for the bone loss associated with postmenopausal osteoporosis and rheumatoid arthritis. NF-κB inducing kinase (NIK) controls activation of the alternative NF-κB pathway, a critical pathway for OC differentiation. Under basal conditions, TRAF3-mediated NIK degradation prevents downstream signaling, and disruption of the NIK:TRAF3 interaction stabilizes NIK leading to constitutive activation of the alternative NF-κB pathway.. Using transgenic mice with OC-lineage expression of NIK lacking its TRAF3 binding domain (NT3), we now find that alternative NF-κB activation enhances not only OC differentiation but also OC function. Activating NT3 with either lysozyme M Cre or cathepsinK Cre causes high turnover osteoporosis with increased activity of OCs and osteoblasts. In vitro, NT3-expressing precursors form OCs more quickly and at lower doses of RANKL. When cultured on bone, they exhibit larger actin rings and increased resorptive activity. OC-specific NT3 transgenic mice also have an exaggerated osteolytic response to the serum transfer model of arthritis.. Constitutive activation of NIK drives enhanced osteoclastogenesis and bone resorption, both in basal conditions and in response to inflammatory stimuli.

Topics: Animals; Arthritis; Binding Sites; Blotting, Western; Bone Density; Bone Marrow Cells; Cathepsin K; Cells, Cultured; Female; Macrophages; Male; Mice; Mice, Transgenic; Muramidase; NF-kappa B; NF-kappaB-Inducing Kinase; Osteocalcin; Osteoclasts; Osteolysis; Osteoporosis; Protein Binding; Protein Serine-Threonine Kinases; RANK Ligand; Reverse Transcriptase Polymerase Chain Reaction; TNF Receptor-Associated Factor 3

Rheumatoid arthritis was diagnosed in a 30-year-old woman with erythema nodosum and arthritic symptoms since 1994, and she was treated with anti-rheumatic agents. Mediastinal and bilateral hilar lymphadenopathy and abnormal pulmonary shadows were detected in 1996, and she was admitted to our hospital in 1997. We also recognized the elevation of ACE and lysozyme, and found granulomas in a transbronchial lung biopsy and an arthrosis synovia biopsy. From these findings, sarcoidosis was diagnosed. Sarcoidosis demonstrating erythema nodosum, arthritis, and bilateral hilar lymphadenopathy is called Löfgren's syndrome. In Caucasians, Löfgren's syndrome is frequently encountered, but it is rare in Japanese. Our case had coexisting arthrosis symptoms, and satisfied the diagnosis criteria of rheumatic arthritis. Therefore, the differential diagnosis was important. We emphasize that it is necessary to consider Löfgren's syndrome when diagnosing patients with rheumatic features, even in Japan.

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Biomarkers; Diagnosis, Differential; Erythema Nodosum; Female; Humans; Lung; Lymphatic Diseases; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis; Syndrome; Synovial Membrane; Tomography, X-Ray Computed

Recent studies indicated that the nicotinamide dinucleotide phosphate oxidase (NADPH) oxidase-derived oxygen radicals plays a deleterious role in arthritis. To study this in more detail, gonarthritis was induced in NADPH oxidase-deficient mice. Mice received an intraarticular injection of either zymosan, to elicit an irritant-induced inflammation, or poly-L-lysine coupled lysozyme, to evoke an immune-complex mediated inflammation in passively immunized mice. In contrast to wild-type mice, arthritis elicited in both p47phox(-/-) and gp91(-/-) mice showed more severe joint inflammation, which developed into a granulomatous synovitis. Treatment with either Zileuton or cobra venom factor showed that the chemokines LTB4 and complement C3 were not the driving force behind the aggravated inflammation in these mice. Arthritic NADPH oxidase-deficient mice showed irreversible cartilage damage as judged by the enhanced aggrecan VDIPEN expression, and chondrocyte death. Furthermore, only in the absence of NADPH oxidase-derived oxygen radicals, the arthritic joints showed osteoclast-like cells, tartrate-resistant acid phosphatase (TRAP)-positive/multinucleated cells, extensive bone erosion, and osteolysis. The enhanced synovial gene expression of tumor necrosis factor-alpha, interleukin-1alpha, matrix metalloproteinase (MMP)-3, MMP-9 and receptor activator of NF-kappaB ligand (RANKL) might contribute to the aggravated arthritis in the NADPH oxidase-deficient mice. This showed that the involvement of NADPH oxidase in arthritis is probably far more complex and that oxygen radicals might also be important in controlling disease severity, and reducing joint inflammation and connective tissue damage.

Topics: Animals; Arthritis; Arthrography; Cartilage, Articular; Connective Tissue; Drug Combinations; Granuloma; Immunization, Passive; Injections, Intra-Articular; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Knee Joint; Matrix Metalloproteinases; Membrane Glycoproteins; Mice; Mice, Knockout; Muramidase; NADPH Oxidase 2; NADPH Oxidases; Phosphoproteins; Polylysine; RNA, Messenger; Sialoglycoproteins; Synovial Membrane; Synovitis; Tissue Inhibitor of Metalloproteinases; Zymosan

Metallothioneins (MTs) are low-molecular-weight cytosolic proteins, which are thought to participate in metal homeostasis and protection against metal toxicity and oxidative stress. MT synthesis can be induced by a variety of inflammatory mediators and antirheumatic drugs, and high levels of MT have been implicated in resistance of cells to some antirheumatic drugs. We studied the expression and localization of MT in synovial tissue samples from patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or osteoarthritis (OA) by quantitative immunohistochemistry. Immunostaining for MT was detected in a large number of intimal lining cells in most of the investigated synovial tissue samples (75%). In a smaller proportion of samples (42%), some of the fibroblast-like cells of the subsynovial layer were also MT positive. Immunostaining and double-staining experiments with antibodies against monocyte-, macrophage- and leucocyte-associated antigens suggested that most of the MT-positive cells were intimal fibroblast-like cells and subsynovial fibroblasts. However, there were no statistically significant differences in the intensity of staining for MT between the rheumatic diseases and OA at the single-cell level. Thus, MT is expressed in synovial tissue and may participate in homeostatic and protective functions. The interindividual variability in the expression of MT in synovial tissue may be related to the therapeutic efficacy of the gold compounds and chemotherapeutic antirheumatic drugs sequestered by MT.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; Arthritis; Arthritis, Psoriatic; Arthritis, Rheumatoid; Child; Female; Humans; Immunohistochemistry; Joint Diseases; Male; Membrane Glycoproteins; Metallothionein; Mice; Middle Aged; Muramidase; Osteoarthritis; Spondylitis, Ankylosing; Synovial Membrane

Intravenous (i.v.) injection of an antigen before immunization has been shown to be a potent way to induce suppression at the T-cell level. In this study we demonstrate an almost complete suppression of arthritis (using antigen-induced arthritis as a model) by i.v. injection of 100 micrograms hen egg lysozyme (HEL) 7 days before immunization. Underlying mechanisms, including suppression by CD8+ T lymphocytes, suppression by T-helper 2 (Th2) or anergy of antigen-specific T lymphocytes, were studied. In vivo treatment with either anti-CD8 or anti-interleukin-4 (IL-4) could not abrogate i.v.-induced tolerance. Lymphocyte stimulation assays showed reduced antigen-specific proliferative responses and IL-2 production in tolerized mice. The possible role of soluble suppressive cytokines was examined in vitro by adding anti-IL-4, anti-IL-10 or anti-transforming growth factor-beta (TGF-beta). Neutralization of these factors could not diminish suppression. Finally, anergy of antigen-specific T lymphocytes was tested as a possible mechanism for i.v.-induced tolerance. Results demonstrated that reduced proliferative T-cell responses were reversible: incubation of tolerized lymph node cells for 5 days in added recombinant (r)IL-2 fully restored proliferative capacity back to normal. We therefore conclude that the main mechanism of i.v.-induced tolerance in our model is anergy of antigen-specific T lymphocytes.

Topics: Animals; Antigens; Arthritis; Cell Division; Clonal Anergy; Epitopes; Female; Injections, Intravenous; Interleukin-2; Interleukin-4; Mice; Mice, Inbred C57BL; Muramidase; T-Lymphocyte Subsets; T-Lymphocytes

High levels of many cytokines, including interleukin (IL)-1, IL-6 and IL-8, were found in various arthropathies suggesting that they play a role in the pathogenesis of disease, although their relationship with the type and activity of disease is still not clear. The synovial fluid (SF) of 24 patients with rheumatoid arthritis (RA), 19 with psoriatic arthritis (PA) and 33 with osteoarthritis (OA) was analyzed for IL-1 beta, IL-6 and IL-8. The highest concentration of the three cytokines was found in the SF of RA. IL-beta detectable levels (> or = 20 pg/ml) were observed in 8/24 (33.3%) patients with RA, in one patient with PA but in no patient with OA. IL-6 (mean +/- SD) (1610.37 +/- 1781.65 pg/ml) was higher in RA than in PA (672.47 +/- 867.40 pg/ml, p = 0.043) and OA (89.45 +/- 120.52 pg/ml, p = 0.0001). IL-8 (1042.72 +/- 698.64 pg/ml) was higher in RA than in PA (660.36 +/- 625.11 pg/ml, p = 0.03) and OA (89.9 +/- 45.88 pg/ml, p = 0.0001). A correlation between IL-1 beta, IL-6 and IL-8 was found in RA. In all patients a correlation between IL-6 and IL-8 levels was found; moreover, these two cytokines were associated with SF indices of inflammation, such as white blood cells (WBC) count and total protein (TP) concentration. Our findings suggest that these interrelationships play a role in the evolution of more severe erosive arthropathy such as RA.

Topics: Arthritis; Arthritis, Psoriatic; Arthritis, Rheumatoid; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Knee Joint; Leukocyte Count; Male; Muramidase; Osteoarthritis; Synovial Fluid

The induction of tolerance, particularly by intervention before established immunity, is widely accepted. We studied the effects of intravenous (i.v.) administration of hen egg lysozyme (HEL), before as well as after immunization, on a HEL-induced arthritis. Arthritis and also cartilage destruction were almost completely suppressed when 100 micrograms HEL was injected before immunization. Antigen-specific proliferative T cell responses and IL-2 production in vitro were inhibited. Antigen-specific immunoglobulin and IgG1 titres were equal in control and tolerized mice, in contrast to lowered IgG2a titres in tolerized animals. Detailed histological studies showed that the immune complex-dependent polymorphonuclear cell phase (< 24 h after arthritis induction) was equal for control and HEL-injected mice. Only in the T cell-dependent phase of the arthritis (> 24 h), did suppression become pronounced in tolerized mice. I.v. administration of 100 micrograms HEL after immunization could only marginally reduce infiltrate and exudate, and no reduction of cartilage destruction was seen. An elegant way to interfere in an established immunity can be offered by creation of bystander suppression. We show that i.v. administration of HEL followed by triggering with HEL, at the moment either of immunization or of arthritis induction, does not reduce a methylated bovine serum albumin (BSA)-arthritis. We conclude that arthritis can be suppressed almost totally when HEL is injected intravenously before immunization. Treatment after immunization is less effective. The i.v. induced suppression is T cell-mediated and and antigen-specific: no bystander suppression circuit can be generated.

Topics: Animals; Antibody Formation; Arthritis; Dose-Response Relationship, Immunologic; Female; Immune Tolerance; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Muramidase; T-Lymphocytes, Regulatory; Time Factors

T-cell vaccination using antigen-specific lines or clones has been shown to be effective in down-regulating immunity in various experimental autoimmune models. Anti-idiotypic networks developing during differentiation of the immune system are considered to be a safeguard against autoimmunity and these pre-existing networks are supposed to be a prerequisite for successful vaccination. However, the interesting question of feasibility of T-cell vaccination beyond the area of autoimmunity remains to be answered. The present study is the first one providing evidence of successful T-cell vaccination in mice immunized against foreign protein antigens (in this system supposedly no pre-existing network exists). Intraperitoneal (i.p.) administration of hen egg lysozyme (HEL)- and chicken egg albumin (OVA)-specific lymph node cells (LNC) were shown to effectively down-regulate immunity (as measured in a delayed type of hypersensitivity) to HEL and OVA, respectively. In contrast, vaccination was unsuccessful with methylated bovine serum albumin (mBSA)-specific LNC in mBSA immunity. Suppression induced by HEL- and OVA-specific LNC was antigen specific. Unlike the greater part of other studies, in which antigen-specific lines or clones were used, we used draining LNC of immunized mice, which after activation were fixed with glutardialdehyde and injected i.p. 10 days before immunization. Finally, effects of T-cell vaccination were studied in a chronic HEL-induced arthritis. Joint swelling, cell influx and cartilage matrix depletion were significantly less in mice treated with antigen-specific cells. We conclude that successful vaccination is feasible in mice rendered immune to foreign protein antigens using a pool of LNC as source of vaccine, suggesting no necessity of a strong pre-existing network.

Topics: Animals; Antigens; Arthritis; Chronic Disease; Female; Immune Tolerance; Lymph Nodes; Mice; Mice, Inbred C57BL; Muramidase; Ovalbumin; Proteins; Serum Albumin, Bovine; T-Lymphocytes; Vaccination

A novel cationic immune-complex-mediated arthritis (ICA) model was developed in mice. The highly cationic protein lysozyme was coupled to poly-L-lysine (PLL) and injected intra-articularly into the knee joint of the mouse, shortly after systemic administration of specific antibodies. A vehement joint inflammation developed, characterized by severe joint swelling and the influx of predominantly polymorphonuclear (PMN) leukocyte. Unique properties were combined in this protein. First, an excellent retention of the antigen in joint structures was found, facilitating sufficient IC formation in the synovial tissue and at the cartilage surface. Secondly, PLL.lysozyme appeared to be a potent inducer of interleukin-1 (IL-1). Similar IL-1 production was measured at 6 hours, in both immune or nonimmune mice. Neutralization with antibodies against either IL-1 alpha or IL-1 beta revealed that IL-1 alpha was the dominant cytokine. Resident cells were responsible for this IL-1 production since a comparable IL-1 signal was measured after intra-articular injection of PLL.lys in neutropenic mice. We further investigated whether IL-1 and complement factors were involved in the onset of this ICA. Neutralizing the IL-1 production with antibodies directed against IL-1 alpha and beta showed a significant decrease in joint swelling. Complement depletion by cobra venom factor also prevented the onset of arthritis for the greater part. Only a minor swelling remained at 6 hours after eliciting arthritis, which was similar to the swelling after injecting the antigen alone and probably reflects IL-1 mediated inflammation. In this study, the authors show a synergistic action of IL-1 and complement in the onset of cationic ICA. Unique properties of the antigen such as excellent retention and its ability to induce IL-1 are combined within one molecule and make this antigen arthritogenic in the presence of antibodies and complement activation.

Topics: Animals; Antigen-Antibody Complex; Arthritis; Cations; Complement System Proteins; Drug Synergism; Injections, Intra-Articular; Interleukin-1; Knee Joint; Male; Mice; Mice, Inbred C57BL; Muramidase; Polylysine; Reference Values; Synovial Membrane

The aims of the present study were to define, under in vivo conditions, factors governing antigen binding and persistence in the rat joint and to establish a chronic arthritis model by means of a natural polycation. The influence of size as well as charge on antigen handling was examined using a range of chemically cationized proteins and natural polycations. Arthritis was induced by intraarticular challenge in preimmunized rats. Immunofluorescence studies revealed that not only pI, which must exceed pH 8-9, but also molecular size was a decisive parameter: only antigens of more than 40 kD were able to persist for significant periods in joint structures. All existing models of antigen induced chronic arthritis in rodents utilize chemically cationized proteins. We extended this system to natural polycations by showing that lysozyme (pI 11.3; MW 14 kD) in tetrameric, charge conserved form (MW 56 kD) as a model-antigen was able to induce chronic arthritis in the rat. After intraarticular challenge of preimmunized animals the course of inflammation was assessed both by 99mTechnetium-pertechnetate (99mTc) scintigram and from the histology. In contrast to monomeric lysozyme, which evoked only a transient inflammatory response (less than two weeks), tetrameric lysozyme induced a chronic arthritis, which still persisted at day 90. Our results show that the ability of cationic antigens to trigger chronic arthritis is vitally size dependent. This is also the first report of a natural polycation acting as an arthritogen, thus providing an experimental basis justifying the search for cationic microbial antigens in human post infectious reactive arthritis.

Topics: Animals; Antigens; Arthritis; Cations; Disease Models, Animal; Dose-Response Relationship, Drug; Knee Joint; Male; Molecular Weight; Muramidase; Proteins; Rats; Rats, Inbred Strains

Previous studies have shown that chronic murine allergic arthritis can only be induced with cationized BSA, related to excellent retention of the cationic antigen in the joint. We now investigate the impact of size of cationic proteins on their potential to induce this form of arthritis. After intra-articular injection, antigen retention is much enhanced with high molecular weight cationized proteins, like albumin or immunoglobulin, compared to small-sized proteins like myoglobulin and lysozyme. Consequently, severe chronic arthritis was only found with the former ones. The role of size is further substantiated with poly-L-lysine-coupled lysozyme. This derivative shows excellent retention in vivo and causes a chronic destructive arthritis in preimmunized mice, in contrast to the poor arthritis seen with native cationic lysozyme. Control experiments made it clear that antigen retention is the most important denominator and that differences in chronicity are not related to gross variations in T-cell reactivity. Retention studies in vitro revealed that the potential to bind to joint structures is similar for the various proteins, suggesting that in vivo conditions determine size-related differences in antigen clearance. Our data indicate that cationicity per se does not make a protein a proper arthritogen.

Topics: Animals; Antigens; Arthritis; Cations; Male; Mice; Mice, Inbred C57BL; Molecular Weight; Muramidase; Polylysine; Proteins

Purified group A streptococcal peptidoglycan-polysaccharide (PG-PS) fragments were either de-O-acylated, or acetylated and then de-O-acylated to yield N-acetylated PG-PS. Native PG-PS was poorly degraded, N-acetylated PG-PS was extensively degraded, and de-O-acylated PG-PS was only slightly degraded by hen egg white lysozyme. N-acetylated PG-PS was also extensively degraded by human lysozyme and partially degraded by rat serum or rat liver extract. After a single intraperitoneal injection of rats with a sterile, aqueous suspension, all PG-PS preparations induced acute arthritis. The acute arthritis induced by N-acetylated PG-PS was significantly more severe than that induced by native PG-PS; that induced by de-O-acylated PG-PS was of intermediate severity. After the acute reaction, rats injected with native PG-PS developed chronic relapsing erosive synovitis which remained severe for the duration of the experiment (83 days). In contrast, joint inflammation induced by N-acetylated PG-PS resolved within 6 weeks with little evidence of recurrent disease. Chronic arthritis induced by de-O-acylated PG-PS was of intermediate severity. In another assay of arthropathic activity, the arthritis in all rat ankle joints, which had been injected directly with native PG-PS, could be reactivated 3 weeks later by the intravenous injection of a small dose of PG. In contrast, only 50% of the joints initially injected with de-O-acylated PG-PS and none of the joints injected with N-acetylated PG-PS could be reactivated. These studies support the concepts that the resistance of PG-PS to muralytic digestion is crucial for chronic arthropathic activity and that the nature and degree of PG acetylation are important molecular determinants of the phlogistic activities of PG-PS polymers.

Topics: Acetylation; Animals; Antigens, Bacterial; Arthritis; Arthritis, Experimental; Female; Muramidase; Peptidoglycan; Polysaccharides, Bacterial; Rats; Streptococcus pyogenes; Structure-Activity Relationship

Topics: Arthritis; Female; Fingers; Histiocytes; Humans; Immunoenzyme Techniques; Lymphatic Diseases; Middle Aged; Muramidase; Osteolysis; Radiography; Skin; Skin Neoplasms

The experiments on rats have shown that preliminary oral administration of vitamin E significantly suppressed generalization, but not development of adjuvant-induced arthritis. Oral vitamin E administration beginning one day after the onset of arthritis inhibited the development and generalization of the disease. Vitamin E had no effect on serum lysosomal enzyme activity, but markedly depressed lipid peroxidation.

Topics: Animals; Arthritis; Arthritis, Experimental; Arylsulfatases; Body Weight; Depression, Chemical; Drug Evaluation, Preclinical; Lysosomes; Male; Muramidase; Rats; Time Factors; Vitamin E

Peptidoglycan-polysaccharide (PG-PS) fragments were purified from cell walls of group D streptococci (Streptococcus faecium, strains ATCC 9790 and F-24) with a protocol which minimizes autolytic activity and tested for ability to induce arthritis in rats. PG-PS fragments from cell walls of other normal flora bacteria (Peptostreptococcus productus, and Propionibacterium acnes), group A streptococci, and pseudomurein-PS fragments from cell walls of Methanobacterium formicicum, were similarly purified and tested. Upon intraarticular injection into rat ankles, all PG-PS polymers induced acute inflammation; pseudomurein-PS fragments were approximately five times less active than the PG-PS preparations. After intraperitoneal injection, P. acnes PG-PS induced a minimal acute arthritis, Peptostreptococcus productus PG-PS induced a moderately severe acute joint inflammation followed by a mild chronic arthritis, and both group A and group D streptococcal PG-PS induced severe acute arthritis which evolved into chronic, erosive joint disease; pseudomurein-PS fragments were without effect, consistent with a crucial role for the PG moiety of PG-PS. Chronic arthritis induced by group D streptococcal PG-PS subsided after 60 days, whereas that induced by group A streptococcal PG-PS was still active after 128 days. The arthropathic properties of this modest number of common normal flora bacteria suggest that different PG-PS structures derived from the normal flora have the potential to induce a wide range of responses, from transient acute to chronic erosive joint disease.

Topics: Amino Acids; Amino Sugars; Animals; Arthritis; Arthritis, Experimental; Cell Wall; Enterobacteriaceae; Female; Hexoses; Muramidase; Polymers; Rats

Bacterial cell wall induced arthritis is an experimental model of chronic erosive synovitis in which arthritis is induced in rats by a single injection of an aqueous suspension of cell wall fragments from selected Gram-positive bacteria. To understand better the Gram-positive bacterial cell wall characteristics necessary for the induction of chronic arthritis we tested the arthritogenicity of five Gram-positive bacteria which were (1) lysozyme resistant and contained a polyrhamnose peptidoglycan side chain moiety, (2) lysozyme resistant, but had little or no rhamnose in the peptidoglycan, polysaccharide, or (3) neither lysozyme resistant, nor contained rhamnose in their peptidoglycan, polysaccharide. All of the lysozyme resistant cell walls tested induced acute arthritis, but only those cell walls which were both lysozyme resistant and contained rhamnose in their polysaccharide side chain were able to induce chronic arthritis. Cell walls which were neither lysozyme resistant nor contained rhamnose were not arthritogenic. These data suggest that both lysozyme resistance and the rhamnose moiety in the peptidoglycan, polysaccharide side chain play an important role in the induction of chronic arthritis by Gram-positive bacterial cell walls in aqueous suspension.

Topics: Animals; Arthritis; Cell Wall; Disease Models, Animal; Female; Lacticaseibacillus casei; Muramidase; Polysaccharides, Bacterial; Rats; Rats, Inbred Lew; Rhamnose; Structure-Activity Relationship

A single intravenous injection into rats of 0.4 mg of the muralytic enzyme mutanolysin, given as long as 3 d after an arthropathic dose of peptidoglycan-polysaccharide polymers derived from group A streptococci (PG-APS), resulted in a complete resolution of acute arthritis and the prevention of chronic joint disease. When administration of mutanolysin was delayed until 14 d after the injection of PG-APS, a great reduction in the severity of chronic inflammation was still observed. Quantitation of the amount of PG-APS present in the limbs, spleen, and liver by a solid phase enzyme-linked immunoassay indicated that the tissues of mutanolysin-treated rats contained as much PG-APS as tissues of PBS-treated control rats. In addition, rats treated with mutanolysin immediately after receiving an intraperitoneal injection of PG-APS developed a transient limb edema similar to that seen in rats after the injection of PG-APS digested to a small fragment size in vitro with mutanolysin. We hypothesize that mutanolysin acts in vivo by degrading PG-APS to small fragments that persist but are no longer arthropathic.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Arthritis; Cell Wall; Chronic Disease; Endopeptidases; Female; Injections, Intravenous; Liver; Lymph Nodes; Muramidase; Peptidoglycan; Rats; Rats, Inbred Lew; Spleen; Streptococcus pyogenes; Tarsal Joints

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; Body Weight; Diterpenes; Female; Muramidase; Phenylbutazone; Rats; Rats, Inbred Strains

It was established in rat experiments that adaptation to altitude hypoxia leads to the enhancement of immune response to sheep red blood cells and to an increase in the serum lysozyme level. Adaptation to altitude hypoxia also suppresses adjuvant arthritis and prevents arthritis-induced inhibition of antibody production.

Topics: Acclimatization; Agglutinins; Altitude; Animals; Antibody Formation; Arthritis; Arthritis, Experimental; Erythrocytes; Hemagglutinins; Hypoxia; Male; Muramidase; Rats; Sheep

Topics: Animals; Antibodies, Bacterial; Arthritis; Arthritis, Experimental; Blood Sedimentation; Complement System Proteins; Leukocytes; Male; Muramidase; Phagocytosis; Rats

Topics: Animals; Arthritis; Arthritis, Experimental; Complement System Proteins; Dermatitis, Atopic; Diphtheria Antitoxin; Diphtheria Toxin; Hippocampus; Hypersensitivity, Delayed; Inflammation; Muramidase; Rabbits; Rats; Tuberculin Test; Turpentine

Similar changes in the nonspecific immunity indices were noted in experiments on rats and guinea pigs with adjuvant disease: depression of blood serum bactericidal activity and increase of the lysozyme and complement level, as well as inhibition of the phagocytic activity of leukocytes and production of normal antibodies to O- and Vi-antigens of typhoid bacilli in rats. Changes in disturbances of natural immunity factors in adjuvant disease correlated with the severity of the process in both animal species.

Topics: Animals; Antibodies, Bacterial; Arthritis; Arthritis, Experimental; Blood Bactericidal Activity; Complement System Proteins; Guinea Pigs; Immunity, Innate; Leukocytes; Male; Muramidase; Phagocytosis; Rats; Salmonella typhi

Topics: Animals; Arthritis; Arthritis, Experimental; Blood Platelets; Cell Extracts; Cytarabine; Glucuronidase; Granulocytes; Inflammation; Leukocyte Count; Leukocytes; Muramidase; Mycobacterium; Rats; Time Factors; Tritium; Zymosan

Topics: Alkaline Phosphatase; Animals; Arthritis; Blood Glucose; Diabetes Mellitus, Experimental; Diphenylamine; Disease Models, Animal; Indazoles; Male; Muramidase; Penicillamine; Phenylbutazone; Pyrazoles; Rats; Sulfanilamides; Sulfhydryl Compounds

Topics: Animals; Arthritis; Body Temperature; Chickens; Exudates and Transudates; Female; Glucuronidase; Joints; L-Lactate Dehydrogenase; Latex; Leukocyte Count; Leukocytes; Male; Microspheres; Muramidase; Posture; Time Factors; Uric Acid

Topics: Acetaminophen; Animals; Arthritis; Chickens; Colchicine; Dose-Response Relationship, Drug; Female; Glucuronidase; L-Lactate Dehydrogenase; Leukocytes; Male; Muramidase; Salicylates; Time Factors

Digestion by lysozyme of delipidated cells of Mycobacterium smegmatis liberates a water-soluble immunoadjuvant fraction which is chemically very similar to the water-soluble adjuvant (WSA) obtained previously from purified cell walls, but which contains somewhat more non-peptidoglycan amino acids. The yield of peptidoglycan-arabinogalactan complex is about 10 times greater starting from whole cells than from cell walls. The main biological properties of this "neo-WSA" are described: it increases circulating antibodies to ovalbumin in guinea pigs, it does not produce polyarthritis in rats or induce hypersensitivity to tuberculin, it does not increase susceptibility to histamine or hyperreactivity to endotoxin, and does not produce spleen and liver hypertrophy. Analogous immunostimulant fractions have also been obtained from delipidated cells of Nocardia opaca by lysozyme treatment.

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Arthritis; Cell Wall; Chromatography; Endotoxins; Guinea Pigs; Histamine; Lipid Metabolism; Liver; Mice; Muramidase; Mycobacterium; Nocardia; Ovalbumin; Rats; Spleen; Ultracentrifugation

1. The polyarthritis produced in rats by i.v. inoculation with Mycoplasma arthritidis was made more severe by salicylates.2. The infection increased the erythrocyte sedimentation rate (ESR), serum lysozyme, counts of total white blood corpuscles, polymorphonuclear cells and lymphocytes, haemolytic serum complement (CH 50) and its component C3. Salicylates enhanced the rise in ESR, CH 50 and C3, but suppressed the rise in lymphocytes and even induced a fall.3. Salicylates did not interfere with the development and action of metabolic inhibition antibodies against M. arthritidis, and did not promote the growth of M. arthritidis.4. Rats treated with salicylate during the first infection acquired the same immunity to reinfection as did infected controls.5. Salicylates did not render rats susceptible to M. fermentans which is non-pathogenic to rats, but may be involved in human rheumatoid arthritis.

Topics: Animals; Antigens, Bacterial; Arthritis; Aspirin; Blood Cell Count; Blood Sedimentation; Complement System Proteins; Erythrocytes; Leukocyte Count; Male; Muramidase; Mycoplasma; Mycoplasma Infections; Rats; Salicylates; Time Factors

Topics: Aniline Compounds; Animals; Arthritis; Aspartate Aminotransferases; Copper; Indazoles; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Male; Muramidase; Rats; Sulfhydryl Compounds; Sulfonamides

1. Rats genetically resistant to dextran and other agents producing the anaphylactoid reaction (NR rats), have a higher polymorph count than do rats which react to these agents (R rats).2. NR rats do not develop polyarthritis when a hind paw is injected intradermally with Freund's adjuvant.3. The polyarthritis produced by an intravenous injection of Mycoplasma arthritidis culture develops more slowly in NR rats than in R rats.4. It is not clear whether the higher polymorph count in NR rats is a main factor in determining their resistance to adjuvant-induced arthritis.

Topics: Animals; Arthritis; Complement System Proteins; Dextrans; Drug Hypersensitivity; Freund's Adjuvant; Hematocrit; Horses; Leukocyte Count; Male; Muramidase; Mycoplasma; Rats; Rats, Inbred Strains

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Azathioprine; Barbiturates; Chloroquine; Collagen; Cyclohexanes; Edema; Female; Glucuronidase; Glycoside Hydrolases; Hexosaminidases; Indomethacin; Leukocyte Count; Muramidase; Peptide Hydrolases; Phenylbutazone; Prednisolone; Rats

Topics: Animals; Arthritis; Arthus Reaction; Cell Adhesion; Cell Movement; Complement System Proteins; Connective Tissue; Cytoplasmic Granules; Glucuronidase; Humans; In Vitro Techniques; Inflammation; Microscopy, Electron; Muramidase; Nephritis; Neutrophils; Peroxidases; Phagocytosis; Rabbits

Topics: Aerobiosis; Animals; Arthritis; Chickens; Coagulase; Deoxyribonucleases; Fibrinolysin; Hemolysin Proteins; Lipase; Microbial Sensitivity Tests; Muramidase; Phosphoric Monoester Hydrolases; Poultry Diseases; Staphylococcus; Staphylococcus Phages; Synovial Fluid; Synovitis; Urease

Topics: Acid Phosphatase; Alkaline Phosphatase; Aminopeptidases; Arthritis; Cartilage; Cathepsins; Fructose-Bisphosphate Aldolase; Glutathione Reductase; Humans; Joints; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Malate Dehydrogenase; Muramidase; Pyruvate Kinase; Spondylitis, Ankylosing; Synovial Fluid

Topics: Animals; Anti-Inflammatory Agents; Antibodies; Arthritis; Aspirin; Body Weight; Cyclophosphamide; Disease Models, Animal; Freund's Adjuvant; Hindlimb; Immunosuppressive Agents; Indomethacin; Male; Methotrexate; Muramidase; Phenylbutazone; Prednisolone; Rats

Topics: Arthritis; Fibrinolysin; Glucose; Humans; Muramidase; Ovalbumin; Peptide Hydrolases; Phosphoric Monoester Hydrolases; Synovial Fluid; Synovial Membrane; Transaminases

Topics: Adrenalectomy; Animals; Anti-Inflammatory Agents; Arthritis; Aspirin; Blood Proteins; Edema; Freund's Adjuvant; Hindlimb; Hot Temperature; Hypophysectomy; Indomethacin; Lysosomes; Male; Muramidase; Paramethasone; Phenylbutazone; Protein Denaturation; Rats; Spectrophotometry; Starch; Stress, Physiological

Topics: Arthritis; Exudates and Transudates; Humans; Injections, Intra-Articular; Joint Diseases; Muramidase; Spectrophotometry; Thiotepa