ANTI-INTEGRIN ANTIBODIES INDUCE TYPE-IV COLLAGENASE EXPRESSION IN KERATINOCYTES

During wound healing, pericellular proteolysis is thought to be essent ial for the detachment of keratinocytes from basement membrane and in their migration into the wound bed. We have characterized integrin-typ e cell adhesion/migration receptors in human mucosal keratinocytes and examined their function in the regulation of type IV collagenase gene expression. Two major integrins of the beta1 class, alpha2beta1 and a lpha3beta1, were found to function as collagen and fibronectin recepto rs, respectively. Antibodies against beta1 and alpha3 integrin subunit s were found to stimulate the expression of the 92 kDa type IV collage nase severalfold in a dose-dependent manner. Keratinocytes expressed a lso the 72 kDa type IV collagenase, the synthesis of which remained, h owever, unchanged in keratinocytes treated with anti-integrin antibodi es. Stimulation of 92 kDa enzyme was found to be caused directly by an tibody binding to integrins, since Fab-fragments of anti-beta1 antibod ies alone were able to induce collagenase expression in the absence of secondary, clustering antibodies. Antibodies against alpha2beta1 inte grin caused no stimulation. Keratinocytes seeded on different substrat a (plastic, collagen, fibronectin, laminin, or vitronectin) showed equ al induction of type IV collagenase expression. Expression of 92 kDa t ype IV collagenase could not be induced by peptides (GRGDS, GRGES), pr oteins (fibronectin, laminin, fibrinogen, albumin), or antibodies to f ibronectin. We suggest that proteolytic processes around keratinocytes can be regulated by extracellular factors signalling through integrin -type receptors. (C) 1993 Wiley-Liss, Inc.