Human Neutrophil Fcγ Receptors Initiate and Play Specialized Nonredundant Roles in Antibody-Mediated Inflammatory Diseases

Naotake Tsuboi, Kenichi Asano, Michael Lauterbach, Tanya N. Mayadas

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Inflammation mediated by antibody-antigen complexes contributes to autoimmune diseases. Mice deficient in the common Fcγ-chain are protected from IgG-mediated glomerulonephritis and the reverse passive Arthus (RPA) reaction and FcR-bearing macrophages, and mast cells have been assigned primary roles in these processes. Here we demonstrate that neutrophil-selective transgenic expression of the two uniquely human neutrophil Fc gamma receptors (FcγRs), FcγRIIA and FcγRIIIB, in Fcγ-chain-deficient mice restored susceptibility to progressive glomerulonephritis and the cutaneous RPA reaction. FcγRIIIB and FcγRIIA mediated neutrophil accumulation, whereas FcγRIIA alone promoted organ injury. In a model of soluble immune complexes deposited within the vasculature, FcγRIIIB was responsible for neutrophil slow rolling and adhesion whereas in the cremaster RPA, induced by both vascular and tissue soluble immune complexes, FcγRIIA predominated. Thus, human FcγRs on neutrophils serve as molecular links between antibody and immunological disease, with FcγRIIA promoting tissue injury and FcγRIIIB and FcγRIIA displaying specialized context-dependent functions in neutrophil recruitment.

Original languageEnglish
Pages (from-to)833-846
Number of pages14
JournalImmunity
Volume28
Issue number6
DOIs
Publication statusPublished - 13-06-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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