Lyn is essential for Fcγ receptor III-mediated systemic anaphylaxis but not for the arthus reaction

Takae Yuasa, Masao Ono, Takeshi Watanabe, Toshiyuki Takai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The Src family kinase Lyn initiates intracellular signal transduction by associating with a variety of immune receptors such as antigen receptor on B cells and high-affinity Fc receptor (FcR) for immunoglobulin Ig(E) (FcεRI) on mast cells. Involvement of Lyn in the IgE-mediated immediate-type hypersensitivity is well documented, but the physiological significance of Lyn in IgG-dependent, type III low-affinity FcR for IgG (FcγRIII)-mediated responses is largely unknown. In this study, we generated a double-mutant mouse strain deficient in both type II FcR for IgG (FcγRIIB) and Lyn to exclude any involvement of inhibitory signaling by FcγRIIB, which otherwise downregulates FcγRIII-mediated cellular responses. FcγRIIB-deficient but Lyn-sufficient mice served as controls. The Lyn deficiency attenuated IgG-mediated systemic anaphylaxis in vivo, and significantly reduced calcium mobilization and degranulation responses of bone marrow-derived mast cells (BMMCs) in vitro. However, we found that either interleukin 4 or tumor necrosis factor α release by BMMCs was comparable to that from Lyn-deficient and control mice, and the reverse-passive Arthus reaction was equally induced in both mutant mice, indicating that Lyn is not involved in the onset of the IgG-mediated, FcγRIII-dependent late phase responses of mast cells. These findings provide us with insight into distinct signaling mechanisms in mast cells underlying the development of diverse pathologies as well as a therapeutic potential for selective treatment of allergic disorders.

Original languageEnglish
Pages (from-to)563-571
Number of pages9
JournalJournal of Experimental Medicine
Volume193
Issue number5
DOIs
Publication statusPublished - 2001 Mar 5

Keywords

  • Arthus reaction
  • Fc receptor
  • Hypersensitivity
  • Lyn
  • Mast cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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