Happonen Kaisa E, Saxne Tore, Aspberg Anders, Mörgelin Matthias, Heinegård Dick, Blom Anna M
Lund University, Malmö, Sweden.
Arthritis Rheum. 2010 Dec;62(12):3574-83. doi: 10.1002/art.27720.
Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage, where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint disease, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This study was undertaken to investigate the ability of COMP to regulate complement, a capacity that has previously been shown for some other cartilage proteins.
Regulation of complement by COMP was studied using functional in vitro assays. Inter-actions between complement proteins and COMP were investigated by direct binding assay and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and OA patients and healthy controls were measured with a novel enzyme-linked immunosorbent assay.
We found in vivo evidence of complement activation by released COMP in the general circulation of patients with RA, but not patients with OA. COMP induced activation and deposition of C3b and C9 specifically via the alternative pathway of complement, which was attributable to direct interaction between COMP and properdin. Furthermore, COMP inhibited the classical and the lectin complement pathways due to direct interaction with the stalk region of C1q and mannose-binding lectin, respectively.
COMP is the first extracellular matrix protein for which an active role in inflammation has been demonstrated in vivo. It can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP fragments, which may be disease specific.
软骨寡聚基质蛋白（COMP）是软骨的一种结构成分，在软骨中它催化胶原纤维形成。在与活动性关节疾病（如类风湿关节炎（RA）和骨关节炎（OA））相关的软骨周转增加期间，血清中COMP含量升高。本研究旨在探讨COMP调节补体的能力，此前已证明一些其他软骨蛋白具有这种能力。
使用功能性体外试验研究COMP对补体的调节作用。通过直接结合试验和电子显微镜研究补体蛋白与COMP之间的相互作用。采用新型酶联免疫吸附测定法测量RA和OA患者及健康对照者血清和滑液中的循环COMP和COMP-C3b复合物。
我们在体内发现RA患者而非OA患者的全身循环中，释放的COMP可激活补体。COMP通过补体替代途径特异性诱导C3b和C9的激活和沉积，这归因于COMP与备解素之间的直接相互作用。此外，COMP分别通过与C1q的柄部区域和甘露糖结合凝集素直接相互作用，抑制经典补体途径和凝集素补体途径。
COMP是首个在体内被证明在炎症中起积极作用的细胞外基质蛋白。它可在激活一种补体途径的同时，有可能抑制另一种补体途径。这些相互作用的最终结果很可能由释放的COMP片段类型决定，而片段类型可能具有疾病特异性。
