KERATINOCYTES FROM JUNCTIONAL EPIDERMOLYSIS-BULLOSA DO ADHERE AND MIGRATE ON THE BASEMENT-MEMBRANE PROTEIN NICEIN THROUGH ALPHA-3-BETA-1 INTEGRIN

BACKGROUND: Junctional epidermolysis bullosa (JEB) encompasses several genodermatoses characterized by skin blistering, and possibly disturb ed wound healing. Although the molecular defects underlying JEB are no t known, we have demonstrated previously that nicein, an adhesive lami nin-related basement membrane component, is immunologically altered in the very severe JEB of Herlitz type (H-JEB), and was expressed to a l esser extent in skin from patients with inversa JEB (I-JEB). In this s tudy, we assessed adhesion and migration of H-JEB and I-JEB keratinocy tes on exogenous nicein and laminin to get insights on the biologic fu nction defective in JEB skin. EXPERIMENTAL DESIGN: Adhesion of culture d epidermal keratinocytes from H-JEB and I-JEB patients was assayed by quantitation of cell attachment 1 hour after seeding into microtiter wells coated with nicein or laminin, Cell migration and modulation by function-blocking antibodies to integrins was quantified by computer-a ssisted image analysis of the tracks left by the cells in a phagokinet ic assay using gold particles coated with nicein or laminin. RESULTS: In spite of the fact that H-JEB keratinocytes do not produce normal im munoreactive nicein, they were able to adhere on exogenous nicein simi larly to normal and I-JEB keratinocytes which produce nicein. Adhesion of both JEB and normal keratinocytes to laminin was weak compared wit h nicein. At low and high concentations of nicein, a reduced migration response occurred with H-JEB keratinocytes whereas I-JEB cells behave d like their normal counterparts. Integrin alpha 3 beta 1 was dominant ly involved in adhesion and migration of all these cells. Laminin did not support the migration of either JEB or normal keratinocytes. CONCL USIONS: H-JEB and I-JEB keratinocytes which produce no or less nicein than normal keratinocytes are able to adhere and migrate on exogenous nicein. Integrin alpha 3 beta 1 which is specifically involved in migr ation and adhesion of keratinocytes on nicein does not appear altered in JEB. These data indicate that defective nicein rather than modifica tions of the nicein-recognizing receptor play a central role in the pa thogenesis of H-JEB.