CELLULAR SOURCE OF COLLAGENASE AND TIMP-1 IN CARRAGEENAN-INDUCED GRANULOMA

We have examined the occurrence and cellular localization of interstit ial collagenase and TIMP-1 mRNAs in a model of granuloma induced by ca rrageenin in guinea pigs. Granulomas were studied at 4, 7, 10, and 14 days after carrageenin injury using a combined protocol for in situ hy bridization and immunofluorescence. Antivimentin monoclonal antibody w as used to identify fibroblasts. Avidin-FITC and Texas red horse antim ouse IgG were employed for detection of probes and antibody, respectiv ely. Our results showed that during the extracellular matrix deposit p hase (4 and 7 days), interstitial collagenase and TIMP-1 mRNAs were ex pressed only by fibroblasts as demonstrated by the colocalization of m RNA and vimentin. By contrast, during the initiation of the resorptive phase (10 and 14 days), fibroblasts and vimentin-negative cells, prob ably macrophages, expressed collagenase and TIMP-1. This study suggest s that fibroblasts are the cell type expressing interstitial collagena se and TIMP-1 mRNA during all phases of the evolution of carrageenin g ranuloma and that macrophages, by contrast, express the mRNA for the e nzyme and the inhibitor exclusively in the degradative phase. (C) 1994 Academic Press, Inc.