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Many cellular properties are influenced by the surrounding environment of extracellular matrix. To better define the interaction between mononuclear phagocytes and the extracellular matrix components they contact, we studied the effect of various matrices on the biosynthesis and secretion of metalloenzymes and the tissue inhibitor of metalloproteinases in human alveolar macrophages. We found that native and denatured collagen types I and III markedly augmented production of interstitial collagenase (> 25-fold) and increased tissue inhibitor of metalloproteinases to a lesser degree (2.5-fold). In contrast, the biosynthesis of another major secreted macrophage metalloproteinase, 92-kDa gelatinase, was unaffected by contact with extracellular matrices. Furthermore, other matrix components (i.e. type IV collagen, laminin, fibronectin, elastin) failed to induce collagenase production. Maximal stimulation of macrophage collagenase production was achieved with 1-5 micrograms/ml (3-15 x 10(-9) M) denatured collagen in contact with cells for 2 h. Increased biosynthesis of collagenase was detected within 24 h of cell contact with native or denatured collagen and was accompanied by marked induction of collagenase mRNA levels. Our studies of signal transduction mechanisms demonstrated that indomethacin decreased gelatin-induced collagenase production by 90%, with enzyme levels completely restored by the addition of exogenous prostaglandin E2. Prostaglandin E2 was only effective when added within the first 2 h after indomethacin treatment. These results indicate that extracellular matrix can directly influence its remodeling and repair via regulation of the production of metalloenzymes by resident inflammatory cells. Furthermore, matrix-metalloproteinase inductive interactions are both enzyme- and matrix-specific, and are mediated, at least in part, by a prostaglandin-dependent mechanism.
Shapiro et al. (Thu,) studied this question.