Critical but overlapping role of FcγRIII and FcγRIV in activation of murine neutrophils by immobilized immune complexes

Zoltán Jakus, Tamás Németh, J. Sjef Verbeek, Attila Mócsai

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42 Citations (Scopus)

Abstract

Immune complex-induced activation of neutrophils through cell surface FcRs plays a central role in the pathogenesis of autoimmune inflammatory diseases. These diseases are often modeled using genetically modified mice. However, in contrast to the number of studies on human cells, the identity of FcRs involved in immune complex activation of murine neutrophils is at present unknown. Furthermore, little is known about the cellular functions mediated by the recently identified murine FcγRIV. In this study, we tested the identity of FcRs involved in the activation of neutrophils by plate-bound immune complexes, using various knockout mouse strains, function-blocking mAbs, or the combination of both approaches. Activation of murine neutrophils by immobilized IgG immune complexes was abrogated in FcR γ-chain-deficient cells, but not by the single or combined deficiency of the γ-chain-associated FcγRI and FcγRIII, or by blocking Abs against either FcγRIII or FcγRIV alone. However, treatment of FcγRIII-deficient neutrophils with FcγRIV-blocking Abs or simultaneous blocking of FcγRIII and FcγRIV in wild-type cells completely inhibited the immune complex-induced cellular responses. In parallel studies, activation of human neutrophils by immobilized immune complexes was abrogated by blocking Abs against either FcγRIIA or FcγRIIIB alone. Taken together, neutrophil activation by immobilized immune complexes requires the murine FcγRIII/FcγRIV or the human FcγRIIA/FcγRIIIB molecules. Although both of the two human receptors are required for this response, the two murine receptors play overlapping, redundant roles. These results promote our understanding of autoimmune diseases and identify an IgG-dependent cellular function of FcγRIV.

Original languageEnglish
Pages (from-to)618-629
Number of pages12
JournalJournal of Immunology
Volume180
Issue number1
Publication statusPublished - Jan 1 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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