Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema.
Systemic exacerbation of allergic responses, in which mast cells play a critical role, results in life-threatening anaphylactic shock. Sphingosine-1-phosphate (S1P), a ligand for a family of G protein-coupled receptors, is a new addition to the repertoire of bioactive lipids secreted by activated mast cells. Yet little is known of its role in human mast cell functions and in anaphylaxis. We show that S1P(2) receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release. Immunoglobulin E-triggered anaphylactic responses, including elevation of circulating histamine and associated pulmonary edema in mice, were significantly attenuated by the S1P(2) antagonist JTE-013 and in S1P(2)-deficient mice, in contrast to anaphylaxis induced by administration of histamine or platelet-activating factor. Hence, S1P and S1P(2) on mast cells are determinants of systemic anaphylaxis and associated pulmonary edema and might be beneficial targets for anaphylaxis attenuation and prophylaxis.
Oskeritzian
Carole A
CA
Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA. coskerit@vcu.edu
Price
Megan M
MM
Hait
Nitai C
NC
Kapitonov
Dmitri
D
Falanga
Yves T
YT
Morales
Johanna K
JK
Ryan
John J
JJ
Milstien
Sheldon
S
Spiegel
Sarah
S
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000941:Antigens / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000503:physiopathology; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011654:Pulmonary Edema / Q000503:physiopathology*; D049349:Receptors, Lysosphingolipid / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012377:Rodentia; D012867:Skin / Q000378:metabolism; D012879:Skin Physiological Phenomena; D000081025:Sphingosine-1-Phosphate Receptors
D000911:Antibodies, Monoclonal; D000941:Antigens; D018925:Chemokines; D016207:Cytokines; D049349:Receptors, Lysosphingolipid; C477522:S1PR2 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D007073:Immunoglobulin E