The expression of messenger RNA encoding neutral metalloproteinases and the tissue inhibitor of metalloproteinases (TIMP) in human arthritic synovium was evaluated in situ, using RNA probes. Interstitial collagenase and stromelysin were expressed by synovial lining cells in patients with active rheumatoid arthritis (RA). Proteinase messenger RNA was found both in cells expressing mononuclear phagocyte antigens and in cells that were negative for the antigens. TIMP was also expressed predominantly along the synovial lining layer. In highly inflammatory RA, TIMP expression appeared less intense than that of the proteases. In osteoarthritic synovium, TIMP was expressed at easily detectable levels, whereas the expression of collagenase and stromelysin was less prominent. The balance between expression of the metalloproteinases and of the metalloproteinase inhibitor in synovium appears to be altered during inflammation. These results are consistent with the notion that synovium plays different roles in the cartilage damage of RA and of osteoarthritis.
Thrombomodulin is an essential cofactor for the activation of the anticoagulant protein C by thrombin. We have identified the expression of thrombomodulin messenger RNA (mRNA) and protein in peripheral blood monocytes. While untreated monocytes expressed thrombomodulin mRNA by Northern blot analysis, lipopolysaccharide-treated cells had decreased mRNA expression. Thrombomodulin antigen was shown in the cytoplasm and on the surface of monocytes by immunohistochemical staining, and thrombomodulin activity was shown on the surface of intact monocytes. One population of synovial lining cells that normally expressed mononuclear phagocyte antigens also expressed thrombomodulin in both noninflamed osteoarthritic synovium and in inflamed rheumatoid arthritis synovium. However, these cells did not express another endothelial protein, von Willebrand factor. We conclude that both circulating and tissue mononuclear phagocytes are capable of expressing thrombomodulin.
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