title: Role of FcRs in animal model of autoimmune bullous pemphigoid.
abstract: Bullous pemphigoid (BP) is a bullous dermatosis associated with autoantibodies directed against the hemidesmosomal Ags BP180 and BP230. Lesional skin is characterized by detachment of the epidermis from the dermis with an intense inflammatory cell infiltrate in the upper dermis. In experimental BP, subepidermal blistering is triggered by rabbit anti-murine BP180 (mBP180) IgG and depends upon complement activation, mast cell degranulation, and neutrophil infiltration. In this study, we determined the role of Fc gammaRs on neutrophils in experimental BP. Mice deficient in Fc gammaRIII (Fc gammaRIII-/-) and those deficient in both Fc gammaRI and Fc gammaRIII (Fc gammaRI&III-/-) but not in Fc gammaRII (Fc gammaRII-/-) were resistant to BP. Pathogenic IgG activated wild-type neutrophils, but not Fc gammaRIII-deficient neutrophils, to secrete proteolytic enzymes. The function of anti-mBP180 IgG depended entirely on its Fc domain; F(ab')2 of IgG had no pathogenic activities. In wild-type mice injected with pathogenic IgG, an Fc gammaR blocker abolished the BP phenotype and inhibited activation of wild-type neutrophils stimulated by pathogenic IgG. Results from this study establish that Fc gammaRIII plays a critical role in the activation of infiltrating neutrophils and the subsequent blistering in experimental BP.
authors.affiliation: Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
authors.forename: Minglang
authors.initials: M
authors.lastname: Zhao
authors.forename: Mary E
authors.initials: ME
authors.lastname: Trimbeger
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Steven D
authors.initials: SD
authors.lastname: Shapiro
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019276:Glycocalyx; D007074:Immunoglobulin G / Q000276:immunology; D008407:Mast Cells / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010391:Pemphigoid, Bullous / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011961:Receptors, Fc / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D011961:Receptors, Fc