The quantity and duration of FcRγ signals determine mast cell degranulation and survival

Sho Yamasaki, Eri Ishikawa, Masayuki Kohno, Takashi Saito

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Immunoglobulin E (IgE) bound to multivalent antigen (Ag) elicits mast cell degranulation but not survival; on the contrary, IgE in the absence of Ag (IgE(-Ag)) induces survival only but not degranulation. Although these distinct responses are mediated through the same receptor, FcεRI, the molecular mechanism generating the divergence is largely unknown. We recently showed that the signals through FcRγ chain are essential for IgE(-Ag)-induced mast cell survival as well as IgE(+Ag)-induced degranulation. To determine whether the cellular output is regulated by the quantity of FcRγ signal, we expressed CD8/FcRγ chimeras (CD8/γ) in bone marrow-derived mast cells (BMMCs) from FcRγ-/- mice to manipulate the strength of FcRγ signals by anti-CD8 cross-linking. Cross-linking of CD8/γ induced mast cell survival and degranulation. Survival was induced by weaker stimulation than needed for degranulation in terms of anti-CD8 concentration and the valency of chimera. However, sustained extracellular signal-regulated kinase (Erk) activation seems to regulate survival even when the activation signal was strong enough to elicit degranulation. Generation of sustained Erk activation by active mitogen-activated protein kinase kinase (MEK) induced BMMC survival. These results suggest that the duration and the magnitude of FcRγ signals may determine mast cell survival and degranulation, respectively.

Original languageEnglish
Pages (from-to)3093-3101
Number of pages9
JournalBlood
Volume103
Issue number8
DOIs
Publication statusPublished - Apr 15 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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