Proteinase inhibitors block formation of pemphigus acantholysis in experimental models of neonatal mice and skin explants: effects of synthetic and plasma proteinase inhibitors on pemphigus acantholysis.
In organ culture experiments, the induction of pemphigus acantholysis is known to be blocked by the addition of serine proteinase inhibitors. Recently, nontoxic synthesized low molecular weight proteinase inhibitors have been clinically available for the treatment of disseminated intravascular coagulation and pancreatitis. To determine if these drugs are useful aids to treat patients with pemphigus, we examined the effect of omega-guanidino ester analogues, i.e., 1) gabexate mesilate, 2) camostat mesilate, and 3) nafamostat mesilate, on experimental pemphigus acantholysis in both organ culture and neonatal BALB/c mice. Furthermore, the effect of plasma natural proteinase inhibitors (alpha-1-proteinase inhibitor) isolated from human plasma was similarly examined. Results revealed that synthesized low molecular weight inhibitors (drugs) were able to inhibit the induction of acantholysis in organ culture system, but had little or no effect on lesion formation in the neonatal mouse system. By contrast, alpha-1-proteinase inhibitor could completely inhibit acantholysis formation in mice. These findings implied a possible new therapeutic approach using proteinase inhibitors for patients with pemphigus.
Naito
K
K
Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan.
Morioka
S
S
Nakajima
S
S
Ogawa
H
H
D000051:Acantholysis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010392:Pemphigus / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011480:Protease Inhibitors / Q000097:blood / Q000138:chemical synthesis / Q000627:therapeutic use*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000517:prevention & control*
D011480:Protease Inhibitors; D010960:Plasminogen Activators; D005341:Fibrinolysin