A major role for neutrophils in experimental bullous pemphigoid.
J Clin Invest
; 100(5): 1256-63, 1997 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Penfigoide Ampolloso
/
Neutrófilos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Clin Invest
Año:
1997
Tipo del documento:
Article
País de afiliación:
Estados Unidos