Simultaneous induction of HSP70 expression, and degranulation, in IgE/Ag-stimulated or extracellular HSP70-stimulated mast cells (129/200)

Abstract

Background

In mast cells, induction of HSP70 expression during antigen stimulation has not been reported.

Methods

Mouse bone marrow derived mast cells (BMMC) were stimulated with IgE/Ag or HSP70. Induction of HSP70 expression, and signaling protein phosphorylation, were evaluated by immunoblotting.

Results

HSP70 expression is induced in BMMC at an early stage of IgE/Ag-dependent stimulation, some of which is released from the cells in a granule-associated form. Induction of HSP70 expression was also observed with an IgE/Ag-stimulated human basophilic cell line, indicating that the phenomenon is not restricted to mouse BMMC. The induction of HSP70 expression, and its release, followed a similar time course to that of degranulation. Released HSP70 seems to be responsible for degranulation and production of eicosanoids, at least in part, since a neutralizing anti-HSP70 antibody mitigated these activities, and since exogenous HSP70 not only induced immediate degranulation followed by autocrine HSP70 expression but also enhanced degranulation in IgE/Ag stimulated BMMC. Extracellular HSP70 was found to induce phosphorylation of Linker for activation of T cells (LAT) and a series of downstream signaling molecules in BMMC. We further found that Fyn, Lyn and spleen tyrosine kinase (Syk), which are known to concern LAT phosphorylation in IgE/Ag stimulated BMMC, were not phosphorylated in HSP70-stimulated BMMC, whereas lymphocyte-specific-protein tyrosine kinase (Lck) was phosphorylated.

Conclusion

FcεRI stimulation in BMMC and basophils induces HSP70 expression and its release. Extracellular HSP70 induces degranulation and mediator release via phosphorylation of LAT.

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