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* Department of Dermatology and
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599; and
Department of Internal Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
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
Rs on neutrophils in experimental BP. Mice deficient in FcRIII (FcRIII–/–) and those deficient in both FcRI and FcRIII (FcRI&III–/–) but not in FcRII (FcRII–/–) were resistant to BP. Pathogenic IgG activated wild-type neutrophils, but not FcRIII-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 FcR blocker abolished the BP phenotype and inhibited activation of wild-type neutrophils stimulated by pathogenic IgG. Results from this study establish that FcRIII plays a critical role in the activation of infiltrating neutrophils and the subsequent blistering in experimental BP.
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1 This work was supported in part by U.S. Public Health Service Grants AI40768 and AI61430 (to Z.L.), AR052109 (to N.L.), and R01 AR-32599 and R37-AR32081 (to. L.A.D.). M.E.T. received a research fellowship grant from the Holderness Foundation.
2 M.Z. and M.E.T. made equal contributions to this work.
3 Address correspondence and reprint requests to Dr. Zhi Liu, Department of Dermatology, University of North Carolina, 3100 Thurston-Bowles, Chapel Hill, NC 27599. E-mail address: zhiliu{at}med.unc.edu
4 Abbreviations used in this paper: BP, bullous pemphigoid; BMZ, basement membrane zone; DEJ, dermal-epidermal junction; NE, neutrophil elastase; MMP, matrix metalloproteinase; mBP180, murine BP180; WT, wild type; KO, knockout; IF, immunofluorescence; i.d., intradermal; PMN, polymorphonuclear leukocyte; MPO, myeloperoxidase; MC, mast cell.
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