REEPITHILIALIZATION OF NORMAL HUMAN EXCISIONAL WOUNDS IS ASSOCIATED WITH A SWITCH FROM ALPHA-V-BETA-5 TO ALPHA-V-BETA-6 INTEGRINS

During cutaneous wound repair, keratinocytes move laterally across the wound surface. For this lateral movement epidermal cells must disasse mble their tenacious connections to the basement membrane and their ne ighbouring cells, and express surface receptors that permit translocat ion over the wound surface extracellular matrix. If the basement membr ane is disrupted, the epidermis migrates over a provisional matrix tha t contains fibrinogen, fibronectin, vitronectin and tenascin. Although alpha 5 beta 1 integrin, a fibronectin receptor, is expressed by huma n epidermis during reepithelialization of excisional and incisional wo unds, the spatial and temporal patterns of vitronectin, tenascin, and other fibronectin receptors are less clear. Other potential receptors include alpha v beta 5 for vitronectin and alpha v beta 6 for fibronec tin and tenascin. To study provisional matrix integrin expression duri ng human wound healing, full-thickness 4-mm punch biopsies were perfor med on the inner surface of the upper arm in adult volunteers. At 3, 7 and 14 days after injury wound sites were excised, bisected, quick fr ozen in liquid nitrogen, and examined for the expression of alpha 5 be ta 5, alpha v, beta 5 and beta 6. At 3 days, alpha 5 beta 1 and alpha v beta 5, but not alpha v beta 6, appeared around the basal and suprab asalar cells of the migrating epidermis. At 7 days, alpha 5 beta 1, al pha v beta 5, and alpha v beta 6 appeared around the perimeter of the basal cells of the migrating epidermis. By 14 days, when re-epithelial ization was complete, all basal and suprabasalar cells overlying the w ound expressed alpha 5 beta 1 and alpha v beta 6, but not alpha v beta 5. Thus, alpha v appeared to switch its heterodimeric association fro m beta 5 to beta 6 subunit during re-epithelialization.