Interrogation of sphingosine-1-phosphate receptor 2 function in vivo reveals a prominent role in the recovery from IgE and IgG-mediated anaphylaxis with minimal effect on its onset

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• 作者：Ana Olivera ; ^{oliveraa@ep.niams.nih.gov} ; Sandra E. Dillahunt ; Juan Rivera ; ^{juan_rivera@nih.gov}
• 关键词：Ag ; antigen ; ABCC1 ; mutidrug resistance-associated protein 1 ; BMMC ; bone marrow derived mast cell ; GPCRs ; G-protein coupled receptors ; DNP ; 2 ; 4-dinitrophenyl ; Fc?RI ; high affinity receptor for IgE ; IL-3 ; interleukin 3 ; LAD2 ; skin-like human mast cell lin
• 刊名：Immunology Letters
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：150
• 期：1-2
• 页码：89-96
• 全文大小：885 K

文摘

Autocrine stimulation of S1PR₂, a receptor for the lipid mediator sphingosine-1-phosphate (S1P), has been implicated in mast cell degranulation to IgE/antigen (Ag) although, paradoxically, its ligand cannot trigger substantial degranulation. Additionally, the in vivo role of S1PR₂ in the overall allergic responses is unclear since S1PR₂ was reported to be required for the onset of systemic anaphylaxis by IgE/Ag but, in apparent contradiction, also for the recovery from histamine-induced anaphylaxis in a mast cell independent manner. Here, we sought to clarify the role of S1PR₂ in mast cell degranulation and in IgE and IgG-mediated anaphylaxis. Lack of S1PR₂ reduced IgE/Ag-induced degranulation in in vitro experiments with mucosal mast cells, but had no effect on connective tissue type mast cells. This latter response correlated with a lack of involvement of S1PR₂ in the onset of non-lethal IgE/Ag-mediated systemic and cutaneous anaphylaxis. However, S1pr2^?/? mice were slow to recover (or did not recover) from Fc?RI-mediated anaphylaxis, an outcome that mirrored their known impairment in histamine clearance due to defective vascular tone. A minor role for S1PR₂ in mast cell degranulation was uncovered upon engagement of low affinity receptors for IgG and in the onset of IgG-mediated anaphylaxis. Our findings show that S1PR₂ is dispensable for initiating IgE/Ag-mediated connective tissue mast cell degranulation and anaphylaxis, but it is required for normal recovery from anaphylaxis.