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J. Exp. Med.,
Volume 188, Number 3, August 3, 1998 475-482
By
From the * Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, and the Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295; the Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease characterized by
deposition of autoantibodies at the basement membrane zone. In an experimental BP model in
mice, the subepidermal blistering is mediated by antibodies directed against the hemidesmosomal protein BP180 (collagen XVII, BPAG2), and depends on complement activation and
neutrophil infiltration. Gelatinase B is present in BP blister fluid and can cleave BP180. In this
study we investigated the role of gelatinase B in the immunopathogenesis of experimental BP
using mice containing targeted disruption of the gelatinase B (MMP-9, 92 kD gelatinase) gene. Gelatinase B-deficient mice were resistant to the blistering effect of intracutaneous anti-mBP180 antibodies, although these mice showed deposition of autoantibodies at the basement
membrane zone and neutrophil recruitment to the skin comparable to that observed in the
control mice. Interleukin 8 given intradermally concomitantly with pathogenic anti-mBP180
elicited a significant neutrophil recruitment into the skin in gelatinase B-deficient mice, but blistering did not occur. However, gelatinase B-deficient mice reconstituted with neutrophils
from normal mice developed blistering in response to anti-mBP180 antibodies. These results
implicate neutrophil-derived gelatinase B in the pathogenesis of experimental BP and might
lead to novel therapeutic strategies for BP.
Department of Medicine,
Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri 63110;
and the § Department of Anatomy, University of California, San Francisco, California 94143
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