Simultaneous induction of HSP70 expression, and degranulation, in IgE/Ag‐stimulated or extracellular HSP70‐stimulated mast cells.

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, because a neutralizing anti‐HSP70 antibody mitigated these activities and because 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. [ABSTRACT FROM AUTHOR]