STIMULATION OF THE COLLAGEN METABOLISM OF ARTICULAR CHONDROCYTES IN CULTURE BY A FACTOR DERIVED FROM POLYMORPHONUCLEAR LEUKOCYTES

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In order to elucidate the pathogenesis of cartilage destruction in joint diseases, the effect of polymorphonuclear leukocytes (PMNs) on the collagen metabolism in chondrocyte culture was investigated. For this purpose, a simple method for the purification of PMNs from peritoneal exudate cells was developed. The method is based on discontinuous density gradient centrifugation in a Ficoll-Urografin system. Extracts of peritoneal PMNs significantly induced chondrocyte collagenase production, change of the cells to fibroblastic form, and the loss of metachromasia (toluidine blue staining). These effects of PMN extract on the chondrocyte culture were reversible; cells of the fibroblastic form were restored to the original polygonal form by replacing the medium with fresh medium containing no PMN extract, and collagenase production ceased. PMNs from peripheral blood did not show any of this activity, suggesting that PMNs acquire the factor(s) during and/or following infiltration from the blood stream into inflamed tissues. The estimated molecular weight of the factor(s) inducing morphological change and collagenase production of chondrocytes was approximately 15,000—20,000, based on gel filtration. The same effluent fraction induced both collagenase production and morphological change of synovial cells. PMN extract suppressed collagen production in chondrocytes to about 60 % of the control, but not production of non-collagenous proteins. The results suggest that PMNs are involved in pathological destruction of articular cartilage by shifting the balance of collagen metabolism in chondrocytes to the catabolic phase.