title: Transactivation of sphingosine-1-phosphate receptors by FcepsilonRI triggering is required for normal mast cell degranulation and chemotaxis.
abstract: 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 S1P1 and S1P2 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 S1P1 and Gi signaling are important for cytoskeletal rearrangements and migration of mast cells toward antigen, they are dispensable for FcepsilonRI-triggered degranulation. However, S1P2, 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.
authors.affiliation: Department of Biochemistry, Virginia Commonwealth University Medical Center, Richmond 23298, USA.
authors.forename: Puneet S
authors.initials: PS
authors.lastname: Jolly
authors.forename: Meryem
authors.initials: M
authors.lastname: Bektas
authors.forename: Ana
authors.initials: A
authors.lastname: Olivera
authors.forename: Claudia
authors.initials: C
authors.lastname: Gonzalez-Espinosa
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
authors.forename: Sheldon
authors.initials: S
authors.lastname: Milstien
authors.forename: Sarah
authors.initials: S
authors.lastname: Spiegel
mesh_terms: D000818:Animals; D001483:Base Sequence; D015550:Cell Degranulation; D002460:Cell Line; D002633:Chemotaxis; D008246:Lysophospholipids / Q000096:biosynthesis; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017455:Receptors, IgE / Q000378:metabolism*; D049312:Receptors, Lysophospholipid; D013110:Sphingosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D015533:Transcriptional Activation
chemical_list: D008246:Lysophospholipids; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D017455:Receptors, IgE; D049312:Receptors, Lysophospholipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine