Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line.
We showed previously that pemphigus IgG enhanced both the activity of urokinase plasminogen activator (uPA) in cultured cells and the expression of its receptor (uPAR) on uPA-binding keratinocytes. In the present study, to clarify whether uPAR and uPA-activated plasmin are actually involved in the blistering process after pemphigus IgG binding to the cell surface, we examined the effects of the following on uPAR expression and on cell-cell detachment in DJM-1 cells, a squamous cell carcinoma line: (i) phosphatidylinositol-specific phospholipase C (PI-PLC) - which releases uPAR from the membrane surface into the culture medium by cleaving the glycosylphosphatidylinositol anchor thus inhibiting uPAR activity, and (ii) uPA inhibitors (tranexamic acid, aprotinin, p-aminobenzonic acid and dexamethasone). Preincubation with PI-PLC decreased dramatically the pemphigus IgG-induced uPAR expression in a dose-dependent manner, and inhibited pemphigus IgG-induced cell-cell detachment at 10 microg/mL. On the other hand, tranexamic acid (15 mM) inhibited pemphigus IgG-induced cell-cell detachment without reduction of uPAR expression, although aprotinin, p-aminobenzonic acid and dexamethasone failed to alter either of these parameters. Although uPAR expression on the pemphigus IgG-bound cell surface and uPA activation may contribute significantly to the pathogenesis of acantholysis in pemphigus, the mechanisms are complicated and should be defined further.
Asano
S
S
Department of Dermatology, Gifu University School of Medicine, Gifu, Japan.
Seishima
M
M
Kitajima
Y
Y
D000051:Acantholysis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D010392:Pemphigus / Q000276:immunology*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000494:pharmacology*
D007074:Immunoglobulin G; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase