Anti‐a2 Integrin Antibody Induces Secretion and Activation of 72‐kDa Progelatinase by Human Fibroblasts

We examined the effects of the extracellular matrix proteins fibronectin, laminin, and matrigel on 72-kDa progelatinase secretion by human lip fibroblasts (KD) and skin fibroblasts (MRC9 and HSF). By gelatin zymography, 1.7 +/- 0.2-fold, 1.7 +/- 0.2-fold, and 1.8 +/- 0.3-fold increases were observed in 72-kDa progelatinase secretion from KD cells treated with fibronectin, laminin, and matrigel, respectively. Laminin and matrigel, but not fibronectin, stimulated 72-kDa progelatinase secretion from HSF cells. Fibronectin, laminin, and matrigel did not stimulate 72-kDa progelatinase secretion by MRC9 cells. Anti-alpha2 integrin antibody-stimulated 72-kDa progelatinase secretion and induced the 62-kDa activated form of 72-kDa progelatinase by KD cells. Activated p42 MAP kinase (MAPK) expression was down-regulated by anti-alpha2 integrin antibody. Anti-alpha2 integrin antibody stimulated 72-kDa progelatinase secretion by HSF cells without inducing the 62-kDa activated form. The data suggest that interaction between fibroblasts and extracellular matrix components via alpha2 integrin plays an important role in regulating secretion and activation of 72-kDa gelatinase and that down-regulation of activated p42 MAPK may be involved in the 72-kDa progelatinase activation mechanism.