Sphingosine‐1‐phosphate can promote mast cell hyper‐reactivity through regulation of contactin‐4 expression

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: Fcɛ;    RI;    mast cell degranulation;    cytokine production;    anaphylaxis;   

DOI  :  10.1189/jlb.0313163

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Bothgenesandtheenvironmentaredeterminantsinthesusceptibilitytoallergiesandmayaltertheseverityofthedisease.WeexploredwhetheranincreaseinthelevelsofthelipidmediatorS1Pinvivo,aconditionfoundduringallergicasthma,couldaffectthesensitivityortheresponseofMCstoIgE/Agandtheonsetofallergicdisease.WefoundthatincreasingS1PlevelsbygeneticdeletionofS1Plyase,theenzymecatabolizingS1P,ledtoelevatedactivityofcirculatingtryptase.Accordingly,MCsofS1Plyase‐deficientmiceweremostlydegranulatedinthetissuesandshowedenhancedcalciumlevels,degranulation,andcytokineproductioninresponsetoIgE/Aginvitro.Th1‐skewedmice(C57BL/6)hadlowerlevelsofS1PincirculationandhistamineresponsesthandidTh2‐skewed(129/Sv)mice.However,whenS1PlevelswereincreasedbypharmacologicinhibitionofS1Plyase,theC57BL/6miceshowedincreasedhistaminereleaseintothecirculationandanaphylacticresponsessimilartothoseinthe129/Svmice.CulturingofMCsinthepresenceofS1Penhancedtheirdegranulationresponses,andwhentheS1P‐treatedMCswereusedtoreconstituteMC‐deficient(KitW‐sh)mice,theycausedenhancedanaphylaxis.GeneexpressionarraysinS1Plyase‐deficientMCsandMCstreatedwithS1Pcontinuouslyrevealedincreasedexpressionofnumerousgenes,includingtheadhesionmoleculeCNTN4,whichcontributedtotheenhancedresponses.OurfindingsarguethatdysregulationinthemetabolismofS1PisacontributingfactorinmodulatingMCresponsivenessandtheallergicresponse...

【 授权许可】

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