Journal article
A major role for neutrophils in experimental bullous pemphigoid
The Journal of clinical investigation, Vol.100(5), pp.1256-1263
09/01/1997
DOI: 10.1172/JCI119639
PMCID: PMC508303
PMID: 9276744
Abstract
Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein, BP180. Using a passive transfer mouse model, our group has shown previously that antibodies to the murine BP180 (mBP180) ectodomain are capable of triggering a blistering skin disease that closely mimics human BP. In this study, we investigated the role of neutrophils in the immunopathogenesis of this disease model. BALB/c mice depleted of circulating neutrophils by treatment with neutrophil-specific antibodies were no longer susceptible to the pathogenic effects of anti-mBP180 IgG. IgG and complement were deposited at the dermal-epidermal junction of these animals, but there was no evidence of inflammatory infiltration or blistering. C5-deficient mice, which are resistant to the pathogenic activity of anti-mBP180 IgG, could be made susceptible to this IgG-mediated blistering disease by intradermal administration of a neutrophil chemoattractant, IL-8 or C5a. Intraperitoneal injection of IL-8, which sequesters neutrophils in the peritoneal cavity, interferes with anti-mBP180-induced neutrophilic infiltration of the skin and prevented the development of BP disease in BALB/c mice. These findings provide the first direct evidence that neutrophils recruited to the skin via a C5-dependent pathway play an essential role in subepidermal blister formation in experimental BP, and suggest new directions for disease intervention.
Details
- Title: Subtitle
- A major role for neutrophils in experimental bullous pemphigoid
- Creators
- Zhi Liu - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.eduGeorge J Giudice - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.eduXiaoye Zhou - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.eduSusan J Swartz - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.eduJames L Troy - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.eduJanet A Fairley - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.eduGerd O Till - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.eduLuis A Diaz - Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. zhiliu@post.its.mcw.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.100(5), pp.1256-1263
- DOI
- 10.1172/JCI119639
- PMID
- 9276744
- PMCID
- PMC508303
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 09/01/1997
- Academic Unit
- Dermatology
- Record Identifier
- 9984025403102771
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