Involvement of urokinase-type plasminogen activator in acantholysis induced by pemphigus IgG.
Pemphigus IgG induces acantholysis in skin organ culture without the involvement of complement. Urokinase-type plasminogen activator, a proteolytic enzyme, has been implicated in the development of acantholysis. To test this hypothesis, we prepared a rabbit anti-urokinase antibody, which inhibited the plasminogen activator activity in normal human epidermis and in cultured keratinocytes. When added to skin organ cultures along with pemphigus IgG, anti-urokinase IgG completely prevented the development of acantholysis. Normal or preimmune rabbit IgG had no effect on pemphigus IgG-induced acantholysis. Plasminogen activator converts the zymogen plasminogen to its active form plasmin, a broad specificity serine proteinase. When high concentrations of plasminogen alone were added to skin organ culture, acantholysis of the pemphigus foliaceous type was induced. Anti-urokinase antibody also inhibited plasminogen-induced acantholysis. These results strongly support a pivotal role for plasminogen activator in the development of acantholysis.
D000051:Acantholysis / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D004817:Epidermis / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007231:Infant, Newborn; D008297:Male; D009924:Organ Culture Techniques; D010392:Pemphigus / Q000201:enzymology / Q000276:immunology* / Q000503:physiopathology; D010960:Plasminogen Activators / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D011817:Rabbits; D012871:Skin Diseases / Q000209:etiology*; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator