Requirement for Vav proteins in post-recruitment neutrophil cytotoxicity in IgG but not complement C3-dependent injury

Ahmad Utomo, Junichi Hirahashi, Divya Mekala, Kenichi Asano, Michael Glogauer, Xavier Cullere, Tanya N. Mayadas

Research output: Contribution to journalArticle

15 Citations (Scopus)


The signals linking neutrophil opsonic receptors, FcγRs and complement receptor 3 (Mac-1) to cellular cytotoxic responses are poorly understood. Furthermore, because a deficiency in activating FcγRs reduces both IgG-mediated neutrophil recruitment and tissue injury, the role of FcγRs specifically in mediating neutrophil cytotoxicity in vivo remains unclear. In this study, we demonstrate that neutrophil Vav 1 and 3, guanine exchange factors for Rac GTPases, are required for IgG/FcγR-mediated hemorrhage and edema in the reverse passive Arthus in the lung and skin. Rac GTPases are also required for development of the reverse passive Arthus reaction. A deficiency in Vav 1 and 3 does not affect neutrophil accumulation at the site of immune complex deposition, thus uncoupling neutrophil recruitment and tissue injury. Surprisingly, Vav and Rac proteins are dispensable for the development of the local Shwartzman reaction in vivo and phagocytosis of complement-opsonized RBC in vitro, processes strictly dependent on Mac-1 and complement C3. Thus, FcγR signaling through the Vav and Rac proteins in neutrophils is critical for stimulating immune complex disease while Vav- and Rac-independent pathways promote Mac-1/complement C3-dependent functions.

Original languageEnglish
Pages (from-to)6279-6287
Number of pages9
JournalJournal of Immunology
Issue number9
Publication statusPublished - 2008 May 1


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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