The quantity and duration of FcRgamma signals determine mast cell degranulation and survival.

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, FcepsilonRI, the molecular mechanism generating the divergence is largely unknown. We recently showed that the signals through FcRgamma 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 FcRgamma signal, we expressed CD8/FcRgamma chimeras (CD8/gamma) in bone marrow-derived mast cells (BMMCs) from FcRgamma(-/-) mice to manipulate the strength of FcRgamma signals by anti-CD8 cross-linking. Cross-linking of CD8/gamma 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 FcRgamma signals may determine mast cell survival and degranulation, respectively.

journal_name

Blood

journal_title

Blood

authors

Yamasaki S,Ishikawa E,Kohno M,Saito T

doi

10.1182/blood-2003-08-2944

subject

Has Abstract

pub_date

2004-04-15 00:00:00

pages

3093-101

issue

8

eissn

0006-4971

issn

1528-0020

pii

2003-08-2944

journal_volume

103

pub_type

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