Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 199, Issue 7, Pages 959-970Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030680
Keywords
sphingosine kinase; SIP receptors; RBL-2H3 cells; motility
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Funding
- NCI NIH HHS [P30 CA16059, P30 CA016059] Funding Source: Medline
- NIAID NIH HHS [AIS0094] Funding Source: Medline
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Mast cells secrete various substances that initiate and perpetuate allergic responses, Cross-linking of the high-affinity receptor for IgE (FcepsilonRI) in RBL-2H3 and bone marrow-derived mast cells activates sphingosine kinase (SphK), which leads to generation and secretion of the potent sphingolipid mediator, sphingosine-1-phosphate (S1P). In turn, S1P activates its receptors S1P, and SIP, that are present in mast cells. Moreover, inhibition of SphK blocks FcepsilonRI-mediated internalization of these receptors and markedly reduces degranulation and chemotaxis. Although transactivation of S1P(1) and Gi signaling are important for cytoskeletal rearrangements and migration of mast cells toward antigen, they are dispensable for FcepsilonRI-triggered degranulation. However, SIP, whose expression is up-regulated by FcepsilonRI cross-linking, was required for degranulation and inhibited migration toward antigen. Together, our results suggest that activation of SphKs and consequently S1PRs by FcepsilonRI triggering plays a crucial role in mast cell functions and might be involved in the movement of mast cells to sites of inflammation.
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