A critical role for neutrophil elastase in experimental bullous pemphigoid. J Clin Invest 2000 Jan;105(1):113-23
Date
01/05/2000Pubmed ID
10619867Pubmed Central ID
PMC382581DOI
10.1172/JCI3693Scopus ID
2-s2.0-0033986322 (requires institutional sign-in at Scopus site) 180 CitationsAbstract
Bullous pemphigoid (BP) is an autoimmune skin disease characterized by subepidermal blisters and autoantibodies against 2 hemidesmosome-associated proteins, BP180 and BP230. The immunopathologic features of BP can be reproduced in mice by passive transfer of anti-BP180 antibodies. Lesion formation in this animal model depends upon complement activation and neutrophil recruitment. In the present study, we investigated the role of neutrophil elastase (NE) in antibody-induced blister formation in experimental BP. Abnormally high levels of caseinolytic activity, consistent with NE, were detected in extracts of lesional skin and blister fluid of mice injected with anti-BP180 IgG. The pathogenic anti-BP180 IgG failed to induce subepidermal blistering in NE-null (NE(-/-)) mutant mice. NE(-/-) mice reconstituted with neutrophils from wild-type mice became susceptible to experimental BP. Wild-type mice given NE inhibitors (alpha1-proteinase inhibitor and Me-O-Suc-Ala-Ala-Pro-Val-CH(2)Cl), but not mice given cathepsin G/chymase inhibitors (alpha1-antichymotrypsin or Z-Gly-Leu-Phe-CH(2)Cl), were resistant to the pathogenic activity of anti-BP180 antibodies. Incubation of murine skin with NE induced BP-like epidermal-dermal detachment. Finally, NE cleaved BP180 in vitro and in vivo. These results implicate NE directly in the dermal-epidermal cleavage induced by anti-BP180 antibodies in the experimental BP model.
Author List
Liu Z, Shapiro SD, Zhou X, Twining SS, Senior RM, Giudice GJ, Fairley JA, Diaz LAAuthor
Sally S. Twining PhD Assistant Dean, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAutoantigens
Carrier Proteins
Collagen
Cytoskeletal Proteins
Dystonin
Humans
Immunoglobulin G
Leukocyte Elastase
Mice
Mice, Inbred BALB C
Nerve Tissue Proteins
Non-Fibrillar Collagens
Pemphigoid, Bullous
Peroxidase
