ALTERED EXPRESSION OF BASEMENT-MEMBRANE PROTEINS AND THEIR INTEGRIN RECEPTORS IN LICHEN-PLANUS - POSSIBLE PATHOGENETIC ROLE OF GELATINASE-AAND GELATINASE-B

Lichenoid lesions of the skin are characterized by a band-like dermal inflammatory infiltrate and structural alterations of the basement mem brane (BM). The etiopathogenesis of these lesions, of which lichen pla nus (LP) is perhaps the prototypic example, is unknown. Acute cases of LP are accompanied by the destruction of epidermal BM, degeneration o f basal keratinocytes with loss of tonofilaments and hemidesmosomes, v esicular alterations, and even blister formation. Chronic LP is charac terized by hyperkeratosis and acanthosis in the epidermis, fibrosis, a nd dense infiltrate in dermis. We found that acute LP lesions are char acterized by uneven or absent immunostaining for laminin-5, laminin-l, and collagen type IV. Distribution and activity of gelatinases matrix metalloproteinase (MMP)-9 and MMP-2, and a specific inhibitor of MMP- 2, tissue inhibitor of metalloprotein-2, were analyzed. The expression and activity of MMP-2 were increased, whereas tissue inhibitor of met alloprotein-2 expression was weak in the involved areas during the acu te phase of LP. Moreover, we demonstrated in vitro that MMP-2 is direc tly capable of digesting laminin-5 gamma 2 chains to yield a 80-kd fra gment. We also observed a weak or absent staining of all examined inte grin receptors in the acute LP lesions. In chronic lesions, the staini ng of BM components was similar to normal controls. in these sections, normal expression of gelatinases and inhibitor was observed. There wa s, however, up-regulation and altered polarity of integrin receptors. These results indicate a link between overexpression of gelatinases, B M disruption, and altered integrin expression. In LP, the digestion of BM by MMP-2 may contribute to the pathogenesis by inducing altered in tegrin expression in basal keratinocytes and ultimately blister format ion.