Konttinen Y T, Lindy O, Kemppinen P, Saari H, Suomalainen K, Vauhkonen M, Lindy S, Sorsa T
Institute of Molecular Immunology, Hospital for Joint Disease, NYU Medical School, New York.
Matrix. 1991 Aug;11(4):296-301. doi: 10.1016/s0934-8832(11)80238-6.
Degradation of cartilage in rheumatoid arthritis (RA) may be in part due to release of collagenase from specific granules of polymorphonuclear neutrophil leukocytes (PMNs) during degranulation. We decided to study, not synovial fluid (SF) collagenase, but PMN collagenase reserves. PMN were isolated from parallel SF and peripheral blood (PB) samples obtained from 7-arthritis patients. PMNs were stimulated in vitro by tetradecanoyl-phorbol-13-acetate (TPA). Collagenase activity in the supernatant without and with phenylmercuric chloride activation was studied. Compared to PB PMNs, there was no consistent decrease in the total collagenase reserves in the inflammatory SF PMNs. This suggests that the release of collagenase in the inflammatory synovial fluid does not deplete SF PMNs of the collagenase synthesized at the myelocyte stage. The role of PMN collagenase in pathogenesis of cartilage destruction would then seem to be more dependent on local release and autoactivation at cartilage surface by adherent PMNs and not excessive collagenase release from free floating SF PMNs at single cell level. Furthermore, under the experimental conditions used the proportion of collagenase released in active form was higher in SF PMN specimens than in PB PMN specimens (p less than 0.01). The predominant collagenous component of adult cartilage, native type II collagen, was degraded by PMN collagenase as fast as native type I collagen. These findings suggest an important role for this enzyme in destruction of the free cartilage surface in RA.
类风湿性关节炎（RA）中软骨的降解可能部分归因于多形核中性粒细胞（PMN）在脱颗粒过程中从特定颗粒释放胶原酶。我们决定研究的不是滑液（SF）胶原酶，而是PMN胶原酶储备。从7名关节炎患者获取的平行滑液和外周血（PB）样本中分离出PMN。用十四烷酰佛波醇-13-乙酸酯（TPA）在体外刺激PMN。研究了有无苯基汞氯化物激活时上清液中的胶原酶活性。与PB PMN相比，炎性SF PMN中的总胶原酶储备没有一致的减少。这表明炎性滑液中胶原酶的释放不会耗尽在髓细胞阶段合成的SF PMN中的胶原酶。那么PMN胶原酶在软骨破坏发病机制中的作用似乎更依赖于黏附的PMN在软骨表面的局部释放和自身激活，而不是游离漂浮的SF PMN在单细胞水平上过度释放胶原酶。此外，在所使用的实验条件下，SF PMN标本中以活性形式释放的胶原酶比例高于PB PMN标本（p小于0.01）。成年软骨的主要胶原成分，天然II型胶原，被PMN胶原酶降解的速度与天然I型胶原一样快。这些发现表明该酶在RA中游离软骨表面破坏中起重要作用。
