INTERSTITIAL COLLAGENASE IS EXPRESSED BY KERATINOCYTES THAT APE ACTIVELY INVOLVED IN REEPITHELIALIZATION IN BLISTERING SKIN DISEASES

Migrating keratinocytes actively involved in reepithelialization in de rmal wounds acquire a collagenolytic phenotype upon contact with the d ermal matrix. To determine whether this phenotype is associated with r epair in other forms of wounds, we assessed collagenase expression in 50 specimens representing a variety of blistering skin diseases, inclu ding subtypes of epidermolysis bullosa, porphyria cutanea tarda, bullo us pemphigoid, pemphigus, transient acantholytic dermatosis, and sucti on blisters. Distinct from that seen in chronic ulcers or in normal he aling by second intention, reepithelialization in these blistering con ditions was not necessarily associated with a complete loss of basemen t membrane, as determined by immunostaining for type IV collagen. Coll agenase mRNA was detected in the basal keratinocytes of several specim ens of epidermolysis bullosa simplex (six of 10) and of pemphigus (thr ee of seven), as well as in one quarter of transient acantholytic derm atosis samples in the presence of an intact basement membrane. In cont rast, three of nine porphyria cutanea tarda, one third of epidermolysi s bullosa acquisita, and one of 10 bullous pemphigoid samples had coll agenase-positive basal keratinocytes with the basement membrane disrup ted. The collagenase-positive lesions generally represented older blis ters with evidence of epithelial regeneration. Collagenase was also ex pressed in suction blisters at 2 and 5 d after induction of the bliste r, but was shut off when the epidermis had healed. Other metalloprotei nases were expressed occasionally, if at all. Our results suggest that keratinocyte migration is associated with collagenase expression and that contact of keratinocytes with the dermal matrix is not necessaril y needed for collagenase induction.