GELATINASE-B IS INVOLVED IN THE IN-VITRO WOUND REPAIR OF HUMAN RESPIRATORY EPITHELIUM

Following epithelial injury, extracellular matrix undergoes imposing r emodelings. We examined the contribution of matrix metalloproteinases, gelatinases A and B, in an in vitro wound repair model of human respi ratory epithelium. Confluent human surface respiratory epithelial (HSR E) cells cultured from dissociated surface cells of human nasal polyps were chemically injured. Over the next 3 to 5 days, cells migrated on to the injured area to repair the circular wound. Repair kinetics of t hese wounds was monitored until wound closure occurred. Gelatinolytic activities were analysed in culture supernates and in cell protein ext racts derived from repairing migratory and non repairing stationary ce lls. Small amounts of gelatinase A were expressed by HSRE cells, and v ariations of this gelatinase remained very weak for the time of the wo und repair. In contrast, gelatinase B was upregulated during the wound repair process, with a maximum peak observed at wound closure. A mark ed gelatinase B activation occurred only in cells involved in the repa ir process. Gelatinase B was localized in some migratory basal cells, recognized by an anti-cytokeratin 14 antibody and located around the w ound. We could not detect any gelatinase A in repairing or in stationa ry HSRE cells. Addition of the 6-6B monoclonal antibody, known to inhi bit gelatinase B activation, to the culture medium during the repair p rocess resulted in a dose-dependent decrease of the wound repair speed . These results suggest that gelatinase B, produced by epithelial cell s, actively contributes to the wound repair process of the respiratory epithelium. (C) 1996 Wiley-Liss, Inc.