CANTHARIDIN-INDUCED ACANTHOLYSIS - ADHESION MOLECULES, PROTEASES, ANDRELATED PROTEINS

Acantholysis is a feature of disorders such as Hailey-Hailey disease a nd Darier's disease. Immunocytochemical studies have shown internaliza tion of desmosomal components after acantholysis. Basal cytokeratins s how suprabasal expression in lesional Darier's disease. The exact mech anisms of acantholysis are still unclear. Cantharidin induces blisteri ng, with suprabasal keratinocyte acantholysis, possibly by protease ac tivation. Plasmin has been implicated in the pathogenesis of acantholy sis in Darier's disease and Hailey-Hailey disease. We examined the dis tribution of desmosomal components, proteases and cytokeratins in cant haridin blisters, to compare them with those previously found in Darie r's disease and Hailey-Hailey disease. Two drops of cantharidin collod ion were applied to the skin of five normal volunteers. A 4-mm punch b iopsy of the blister was taken, and snap frozen. Sections were stained with antibodies to desmosomal proteins (dp) 1/2, dp 3, desmosomal gly coproteins (dg) 1, 2/3, extracellular carbohydrate residues, using the lectins peanut agglutinin (PNA) and soybean agglutinin (SBA), proteas es and cytokeratins. Acantholytic cells were stained diffusely with dp 1/2; there was markedly reduced or absent peripheral staining for dp3, dg1, dg 2/3, PNA and SBA. There was no clumping of stain. Plasminogen , fibrinogen and urokinase were expressed in some acantholytic cells. Basal keratin markers were expressed suprabasally in acantholytic cell s, These results are similar to those previously obtained in Darier's disease, but different from the staining obtained in Hailey-Hailey dis ease. Extracellular glycosylated portions of adhesion molecules may be lost after acantholysis, perhaps as a result of conformational change s, internalization of extracellular domains, or proteolysis. The chang es in the expression of plasminogen, fibrinogen, urokinase and cytoker atins in acantholytic cells in cantharidin-induced blisters are, as in Darier's disease and Hailey-Hailey disease, probably secondary to aca ntholysis, and changes in the shape of cells. We conclude that canthar idin blisters may be a useful model for the study of acantholysis in D arier's disease.