CELL-MATRIX INTERACTIONS MODULATE INTERSTITIAL COLLAGENASE EXPRESSIONBY HUMAN KERATINOCYTES ACTIVELY INVOLVED IN WOUND-HEALING

We reported that interstitial collagenase is produced by keratinocytes at the edge of ulcers in pyogenic granuloma, and in this report, we a ssessed if production of this metalloproteinase is a common feature of the epidermal response in a variety of wounds. In all samples of chro nic ulcers, regardless of etiology, and in incision wounds, collagenas e mRNA, localized by in situ hybridization, was prominently expressed by basal keratinocytes bordering the sites of active re-epithelializat ion indicating that collagenolytic activity is a characteristic respon se of the epidermis to wounding. No expression of mRNAs for 72- and 92 -kD gelatinases or matrilysin was seen in keratinocytes, and no signal for any metalloproteinase was detected in normal epidermis. Immunosta ining for type IV collagen showed that collagenase-positive keratinocy tes were not in contact with an intact basement membrane and, unlike n ormal keratinocytes, expressed alpha5beta1 receptors. These observatio ns suggest that cell-matrix interactions influence collagenase express ion by epidermal cells. Indeed, as determined by ELISA, primary cultur es of human keratinocytes grown on basement membrane proteins (Matrige l; Collaborative Research Inc., Bedford, MA) did not express significa nt levels of collagenase, whereas cells grown on type I collagen produ ced markedly increased levels. These results suggest that migrating ke ratinocytes actively involved in re-epithelialization acquire a collag enolytic phenotype upon contact with the dermal matrix.