Formation of Foregin Body Granuloma Is Associated with MMP/TIMP by Subcutaneous and Intraperitoenal Injection of Mineral fibers In Rats

초록

Matrix metalloproteinase (MMPs) and tissue inhibitor of metalloproteinase (TIMP-2) produced by activated macrophages or fibroblasts, are an important effect molecule in the inflammatory granulomatous or reparative reaction. The focus of this study was to examine changes in expression of MMPs and TIMP-2 in the response to two specific types of fibrous mineral(fibrous talc and crocidolite) generated in Sprague-Dawley female rats. Mineral fibers initially elicited severe inflammatory reaction with necrosis followed by formation of well-delineated nodules composed of granulomas. The size of nodules induced by fibrous talc were larger than that of crocidolite. Fibrous talc resulted in granulomas with more conspicuous giant cell formation and more apparent geographic necrosis than in the lesions induced by crocidolite. MMPs and TIMP-2 was mostly expressed in the cytoplasm of histiocytes scattered within the granulomas. The expression of MMPs was elevated at days 7 or 15 until 60 after injection, when granulomatous lesions formed. TIMP-2 expression was consistently elevated in the lesion of both experimental groups throughout experimental periods. At day 30 of injected, the relative levels of MMP-2 and TIMP-2 had nearly reversed with increased expression of MMP-2 and decreased TIMP-2. Altering the ratio of MMP-2 to TIMP-2 may play a role in down-regulating the activity of MMP-2. But MMP-2 was lower levels in the talc injected model than that of asbestos model during whole experimental periods. Taken together, the data suggest the expression of MMP-2 and MMP-9 were required for promoting granuloma formation and limited tissue destruction. Specific expression of MMPs/TIMP was correlated with grade of tissue destruction or resolution of inflammation and the resulting foreign body reaction by different foreign fibrous mineral.