Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen - PubMed (original) (raw)

. 2005 Mar 1;105(5):2059-65.

doi: 10.1182/blood-2004-07-2639. Epub 2004 Nov 12.

Affiliations

Free article

Rapid and large amount of autocrine IL-3 production is responsible for mast cell survival by IgE in the absence of antigen

Masayuki Kohno et al. Blood. 2005.

Free article

Abstract

Cross-linking FcepsilonRI on mast cells by immunoglobulin E (IgE) and antigen (Ag) initiates cascades leading to antiparasitic or allergic responses. It was recently reported that IgE without antigen, IgE(-Ag), actively promotes mast cell survival. Although we have demonstrated that the immunoreceptor tyrosine-based activation motif within FcRgamma is essential for IgE(-Ag)-induced mast cell survival, the underlying mechanism remains still unclear. Here, we investigated the mechanism of IgE(-Ag)-induced survival using mast cells lacking several downstream molecules. Lyn and Syk were essential, whereas Fyn, Gab2, and the phosphoinositide 3-kinase-Akt pathway were not critical for survival. Failure of survival in FcRgamma-/- bone marrow mast cells (BMMCs) was rescued by coculture with IgE-treated wild-type BMMCs, suggesting that survival is induced not directly through FcepsilonRI signals. We found that the survival is predominantly mediated by high production of interleukin 3 (IL-3), evidenced by severe impairment of survival by anti-IL-3 and in IL-3-/- BMMCs. The up-regulation of Bcl-xL/Bcl-2 by IgE was abrogated in IL-3-/- BMMCs, whereas the expression of histidine decarboxylase was normally induced. These results indicate that IL-3 plays a crucial role for IgE(-Ag)-induced mast cell survival, functioning in an autocrine manner by inducing the Bcl-xL/Bcl-2 via signal transducer and activator of transduction 5. We further suggest that IgE(-Ag)-mediated gene expression in mast cells is regulated at least 2 mechanisms: autocrine IL-3 dependent and independent.

PubMed Disclaimer

Similar articles

Cited by

MeSH terms

Substances

LinkOut - more resources