Imbalance between plasminogen activator and its inhibitors in thiol-induced acantholysis.
Pemphigus may be an idiopathic disease or a syndrome induced by drugs, mainly thiol drugs. Autoantibodies, always present in the idiopathic form but often lacking in the drug-induced one, may cause acantholysis by activating endogenous proteolytic enzymes. Pathogenesis of drug-induced pemphigus when antibodies are absent has not been elucidated yet. Extracts of skin tissues cultured for 4 days with penicillamine, captopril or thiopronine were assayed for the presence of plasminogen activator (PA) and plasminogen activator inhibitors (PAI) on agar fibrin plates. Moreover, uPA, tPA, and PAI-1 were identified in the extracts by immunoenzymatic assay. The results have shown progressively decreasing amounts of PAI-1 in penicillamine, thiopronine and captopril-cultured tissue extracts, respectively. This suggests that the acantholytic potential of thiol drugs is directly correlated to their capability of reducing PAI-1 in the epidermal cells leading to increased PA activity. This PA-PAI imbalance may be itself the cause of intraepidermal splitting.
Lombardi
M L
ML
Servizio di Oncologia Sperimentale C Immunologia, Istituto Nazionale Tumori, Napoli, Italia.
de Angelis
E
E
Rossano
F
F
Ruocco
V
V
D000051:Acantholysis / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002216:Captopril / Q000494:pharmacology; D003470:Culture Media; D046508:Culture Techniques; D004817:Epidermis / Q000201:enzymology / Q000473:pathology; D006801:Humans; D010396:Penicillamine / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D010960:Plasminogen Activators / Q000032:analysis* / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000032:analysis* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000009:adverse effects*; D008625:Tiopronin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000037:antagonists & inhibitors; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000037:antagonists & inhibitors
D003470:Culture Media; D017395:Plasminogen Activator Inhibitor 1; D015849:Plasminogen Inactivators; D013438:Sulfhydryl Compounds; D002216:Captopril; D008625:Tiopronin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D010396:Penicillamine