Dexamethasone inhibits plasminogen activator activity in experimental pemphigus in vivo but does not block acantholysis.
In vitro studies have suggested that autoantibody-stimulated increases in epidermal plasminogen activator (PA) may be an important pathogenetic mechanism in pemphigus vulgaris (PV). We measured PA in murine epidermis after i.p. injection of normal human IgG (NH IgG) and PV IgG, with and without exposure to dexamethasone (DEX). BALB/c neonates received i.p. injections of saline control or DEX (20 mg/kg). Twenty-four hours later, they received a second injection of saline or DEX and a single dose of NH or PV IgG (20 mg/gm body weight). After 24 hr, epidermis was obtained and was sequentially extracted in 0.14 M NaCl, pH 6.8, and 0.5% Triton X-100 in 0.1 M Tris, pH 8.1. Epidermal PA was assayed in the Triton-Tris supernatant by a two-stage colorimetric reaction and was expressed as milliPloug units per milligram of protein (mPu/A280). PA in animals injected with NH IgG was 0.21 +/- 0.11 mPu/A280 (n = 8). Epidermal PA was increased in animals with cutaneous lesions of pemphigus to 0.42 +/- 0.29 (n = 15). Treatment with DEX decreased PA levels in both animals receiving NH IgG and PV IgG by 80%, to 0.04 +/- 0.05 (n = 15) and 0.09 +/- 0.07 (n = 7), respectively. Despite the decreased PA activity, all animals in the PV IgG and the PV IgG-plus-DEX group had identical and extensive cutaneous disease, and lesions developed at the same time points. This finding shows that PV autoantibodies can stimulate increases in epidermal PA, but reduction of PA by corticosteroids does not inhibit acantholysis in vivo. There is no clear correlation between PA and disease activity in the murine model of pemphigus.
Anhalt
G J
GJ
Patel
H P
HP
Labib
R S
RS
Diaz
L A
LA
Proud
D
D
D000051:Acantholysis / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage* / Q000097:blood; D004817:Epidermis / Q000201:enzymology; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D010392:Pemphigus / Q000201:enzymology / Q000209:etiology / Q000276:immunology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D012871:Skin Diseases / Q000276:immunology*
D007074:Immunoglobulin G; D015849:Plasminogen Inactivators; D003907:Dexamethasone; D010960:Plasminogen Activators