MAJOR ROLE FOR NEUTROPHILS IN EXPERIMENTAL BULLOUS PEMPHIGOID

Bullous pemphigoid (BP) is an inflammatory subepidermal blistering dis ease associated with an IgG autoimmune response to the hemidesmosomal protein, BP180, Using a passive transfer mouse model, our group has sh own previously that antibodies to the murine BP180 (mBP180) ectodomain are capable of triggering a blistering skin disease that closely mimi cs 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 antibod ies were no longer susceptible to the pathogenic effects of anti-mBP18 0 IgG, IgG and complement were deposited at the dermal-epidermal junct ion of these animals, but there was no evidence of inflammatory infilt ration or blistering, CS-deficient mice? which are resistant to the pa thogenic activity of anti-mBP180 IgG, could be made susceptible to thi s IgG-mediated blistering disease by intradermal administration of a n eutrophil chemoattractant, IL-8 or C5a, Intraperitoneal injection of I L-8, which sequesters neutrophils in the peritoneal cavity, interferes with anti-mBP180-induced neutrophilic infiltration of the skin and pr evented the development of BP disease in BALB/c mice, These findings p rovide the first direct evidence that neutrophils recruited to the ski n via a CS-dependent pathway play an essential role in subepidermal bl ister formation in experimental BP, and suggest new directions for dis ease intervention.