EFFECT OF POLYMORPHONUCLEAR LEUKOCYTES ON SYNOVIAL CELL COLLAGENASE PRODUCTION

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Abstract
To clarify the roles of inflammatory cells in connective tissue destruction at chronic inflammatory lesions, such as joints with rheumatoid arthritis and collagen-induced arthritis, the effects of [rat] polymorphonuclear (PMN) leukocytes on synovial cells were studied in an in vitro cell culture system. Extracts of peritoneal PMN cells significantly induced synovial cell collagenase production. This inducing factor was also detected in the medium after short-time culture of PMN cells in Dulbecco''s modified Eagle''s medium (D-MEM) containing 10% fetal calf serum (FCS). The release of the factor into the medium was markedly enhanced by the addition of cytochalasin B or foreign particles, suggesting that the factor is released from the granules of PMN cells by exocytosis. The MW of the factor was estimated to be approximately 20,000 daltons. Similar stimulating factors were detected in the cytosol fraction of PMN cells, which comprised 2 molecular sizes corresponding to 20,000 and 45,000 daltons and accounted for approximately 70% of total stimulating activity in the cell. PMN cells are evidently involved in the pathological destruction of the connective tissue at chronic inflammatory joints, not only by releasing their own tissue-degrading enzymes, but also by inducing synovial cell collagenase production.