Journal article
A critical role for neutrophil elastase in experimental bullous pemphigoid
The Journal of clinical investigation, Vol.105(1), pp.113-123
01/01/2000
DOI: 10.1172/JCI3693
PMCID: PMC382581
PMID: 10619867
Abstract
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 (α1-proteinase inhibitor and Me-O-Suc-Ala-Ala-Pro-Val-CH
2
Cl), but not mice given cathepsin G/chymase inhibitors (α1-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.
Details
- Title: Subtitle
- A critical role for neutrophil elastase in experimental bullous pemphigoid
- Creators
- Zhi Liu - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USASteven D Shapiro - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USAXiaoye Zhou - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USASally S Twining - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USARobert M Senior - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USAGeorge J Giudice - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USAJanet A Fairley - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USALuis A Diaz - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.105(1), pp.113-123
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI3693
- PMID
- 10619867
- PMCID
- PMC382581
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 01/01/2000
- Academic Unit
- Dermatology
- Record Identifier
- 9984025570102771
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