Role of plasminogen activator in pemphigus vulgaris.
The role of plasminogen activator (PA) in the pathogenesis of acantholysis in canine pemphigus vulgaris (PV) was evaluated using differentiated cultures of canine oral keratinocytes. Both the secreted and cell-associated PA activity in cultured canine keratinocytes were completely inhibited by specific anti-urokinase antibodies. Anti-tissue type PA antibodies did not inhibit either secreted or cell-associated PA activity. Immunoblots and fibrin zymography revealed a single 57,000 molecular weight urokinase-type PA in the conditioned media of the canine oral keratinocytes. Incubation of the differentiated cultures with PV Ig resulted in a significant increased in the levels of PA activity and both canine and human PV Ig were effective at inducing acantholysis typical of that seen in the clinical disease. The addition of urokinase inhibitor to the cultures treated with PV Ig prevented the development of acantholysis. These data strongly support the conclusion that PA is involved in acantholysis which is the cardinal feature of PV.
Wilkinson
J E
JE
Department of Pathobiology, University of Tennessee, Knoxville 37901.
Smith
C A
CA
Suter
M M
MM
Falchek
W
W
Lewis
R M
RM
D000051:Acantholysis / Q000139:chemically induced; D000818:Animals; D000906:Antibodies / Q000502:physiology; D002478:Cells, Cultured; D004285:Dogs; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D007136:Immunoglobulins; D007633:Keratins; D010392:Pemphigus / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015849:Plasminogen Inactivators; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D000906:Antibodies; D007136:Immunoglobulins; D015849:Plasminogen Inactivators; D007633:Keratins; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator