Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema

被引:96
作者
Oskeritzian, Carole A. [1 ]
Price, Megan M. [1 ]
Hait, Nitai C. [1 ]
Kapitonov, Dmitri [1 ]
Falanga, Yves T. [2 ]
Morales, Johanna K. [2 ]
Ryan, John J. [2 ]
Milstien, Sheldon [1 ]
Spiegel, Sarah [1 ]
机构
[1] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Sch Med, Richmond, VA 23298 USA
[2] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA
基金
美国国家卫生研究院;
关键词
FC-EPSILON-RI; SPHINGOSINE; 1-PHOSPHATE; VASCULAR-PERMEABILITY; LYMPHOCYTE EGRESS; BARRIER INTEGRITY; IN-VIVO; KINASE-1; DEGRANULATION; EXPRESSION; IMMUNITY;
D O I
10.1084/jem.20091513
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:465 / 474
页数:10
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