muramidase and Osteoarthritis

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

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

Neo-synovial membranes, which formed after "primary" synovectomy in 21 patients with rheumatoid arthritis (RA), were studied at resynovectomy. The clinical, histomorphological, and immunohistological data were compared with data derived from "primary" synovial membranes from RA and osteoarthritis (OA) patients. The clinical data suggest a less active rheumatoid inflammatory response after synovectomy. Histomorphologicaly, the synovitis in resynovectomized neosynovial membranes of RA revealed no qualitative differences when compared with synovitis in the "primary" synovium. However, the degree of the inflammatory rection evaluated by the different parameters was found to be distinctly lower. The immunohistological data correlated with these findings.

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Heparin; Humans; Immunohistochemistry; Male; Middle Aged; Muramidase; Osteoarthritis; Radiography; Reoperation; Synovectomy; Synovial Membrane

High activity of proinflammatory, type II phospholipase A2 (PLA2) was found in synovial fluids (SF) in inflammatory arthritis. In search for the sources of this PLA2, we cultured human articular chondrocytes and cartilage explants from healthy, osteoarthritic and rheumatoid joints. All cultures, unstimulated by cytokines, released PLA2 extracellularly. Cultures obtained from the deep layers of the cartilage released more PLA2 than those obtained from the superficial layers. Deep layer explants released 0.38 to 18.16 pmol/min/mg protein PLA2/day, whereas superficial layer explants released 0.39-3.18 pmol/min/mg/day. Chondrocyte cell cultures continuously released PLA2, in the first day 909-46347 pmol/min/(10)6 cells and after 9-26 days of culture 166-2115 pmol/min/10(6) cells. PLA2 released from chondrocytes was calcium dependent and had optimum activity at pH 7.5. Cycloheximide markedly inhibited its release. Chondrocyte cultures also released muramidase (LZM) but there was no correlation between PLA2 and LZM release. It may be concluded that cytokine unstimulated human articular chondrocytes synthesize and release PLA2 extracellularly which is similar to that found in the SF. Thus, chondrocytes may possibly serve as one of the sources of intraarticular PLA2.

Topics: Arthritis, Rheumatoid; Cartilage, Articular; Cells, Cultured; Cycloheximide; Humans; Muramidase; Osteoarthritis; Phospholipases A; Phospholipases A2; Reference Values

A new method for the measurement of lysozyme activity, which is rapid, quantitative and sensitive, was established and applied to clinical material obtained from arthritis patients. The method is based on fluorescence polarization with the use of fluorescein isothiocyanate-labeled peptidoglycan. Using this method, we found that the synovial fluids obtained from rheumatoid arthritis contained more lysozyme activity than similar samples from osteoarthritis patients (P less than 0.001). Furthermore, we found that chemotactic factors and lysozyme-depleted rheumatoid synovial fluids could induce the release of lysozyme from human polymorphonuclear leukocytes in vitro. It is therefore suggested that lysozyme present in rheumatoid synovial fluids may derive in part from polymorphonuclear leukocytes and the action of chemotactic factor(s) within the fluids.

Topics: Arthritis, Rheumatoid; Chemotactic Factors; Female; Fluorescence Polarization; Humans; Muramidase; Neutrophils; Osteoarthritis; Synovial Fluid

Topics: Arthritis, Rheumatoid; Humans; Muramidase; Osteoarthritis; Synovial Fluid

Topics: Arthritis, Rheumatoid; Humans; Leukocytes; Monocytes; Muramidase; Neutrophils; Osteoarthritis; Receptors, Fc; Synovial Fluid; T-Lymphocytes

Lysozyme-producing cells were analysed by enzyme histochemistry in paraffin sections of synovial tissue of 60 patients with rheumatoid arthritis (RA) and 20 patients with osteoarthritis (OA). For lysozyme detection three enzyme histochemical systems - peroxidase-anti-peroxidase, alkaline phosphatase and biotin-avidin - were used in parallel experiments. Lysozyme was found to be produced by polymorphonuclear cells, mononuclear phagocytes and part of synovial lining cells. All types of lysozyme-producing cells were increased in RA compared with OA. Subgrouping of RA synovitis according to histomorphological criteria allowed the demonstration of an inverse relationship between the number of lysozyme-producing cells and the grade of proliferation of fibroblasts, called mesenchymoid transformation by Fassbender [19]. The different methods of lysozyme detection differed in specificity and sensitivity. The immunoenzymatic staining of lysozyme allows specific and quantitative evaluation of phagocytizing cells in RA and OA.

Topics: Arthritis, Rheumatoid; Female; Histocytochemistry; Humans; Male; Middle Aged; Muramidase; Osteoarthritis; Synovial Membrane; Tissue Distribution

1. The permeability of the synovial membrane for proteins is larger in rheumatoid arthritis than in osteoarthrosis, in rheumatoid arthritis with high CRP activity larger than in rheumatoid arthritis with low CRP activity. 2. The diffusion by the synovial membrane in most plasma proteins takes place depending on their molecular weight. Of the 14 proteins tested only haptoglobin and fibrinogen did not follow this regularity. 3. While the non-immune proteins proved in the synovial fluid only come from the blood plasma, the immune globulins IgG, IgA, and IgM as well as lysozyme are partly also locally synthetized and enriched in rheumatoid arthritis. In rheumatoid arthritis lysozyme is present in the synovia not only in free, but in most cases also in cell-bound form.

Topics: Arthritis, Rheumatoid; Blood Proteins; C-Reactive Protein; Humans; Immunoglobulins; Molecular Weight; Muramidase; Osteoarthritis; Permeability; Rheumatic Diseases; Synovial Membrane

Topics: Arthritis, Rheumatoid; Humans; Monoamine Oxidase; Muramidase; Osteoarthritis; Synovial Fluid

Topics: Adult; Aged; Animals; Bone Matrix; Cartilage, Articular; Cattle; Chickens; Female; Humans; Male; Middle Aged; Muramidase; Osteoarthritis; Proteoglycans

Topics: Arthritis, Rheumatoid; Humans; Leukocyte Count; Muramidase; Osteoarthritis; Synovial Fluid

Topics: Adult; Aged; Arthritis, Rheumatoid; Female; Glucuronidase; Glycoside Hydrolases; Hexosaminidases; Humans; Knee Joint; Male; Middle Aged; Muramidase; Osteoarthritis; Synovial Fluid