Altered eosinophil profile in mice with ST6Gal‐1 deficiency: an additional role for ST6Gal‐1 generated by the P1 promoter in regulating allergic inflammation

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

关键词: sialic acid;    sialyltransferase;    myelopoiesis;    Th2;    allergic airway;   

DOI  :  10.1189/jlb.1108704

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CumulativeevidenceindicatesthatthesialyltransferaseST6Gal‐1andthesialyl‐glycans,whichitconstructs,arefunctionallypleiotropic.ExpressionoftheST6Gal‐1geneismediatedbysixdistinctpromoter/regulatoryregions,andwehypothesizedthatthesepromotersmaybeuseddifferentiallytoproduceST6Gal‐1fordifferentbiologicpurposes.Toexaminethishypothesis,wecomparedamousewithacompletedeficiencyinST6Gal‐1(Siat1null)withanothermousethatwehavecreatedpreviouslywithadisruptiononlyintheP1promoter(Siat1ΔP1).WenotedpreviouslygreaterneutrophilicinflammationassociatedwithST6Gal‐1deficiency.Here,wereportthatST6Gal‐1‐deficientmicealsohavesignificantlyelevatedeosinophilicresponses.Uponi.p.thioglycollateelicitation,eosinophilsaccountedforover20%ofthetotalperitonealinflammatorycellpoolinST6Gal‐1‐deficientanimals,whichwasthreefoldgreaterthanincorrespondingwild‐typeanimals.Aprincipalfeatureofallergicrespiratoryinflammationispulmonaryeosinophilia,weevaluatedtheroleofST6Gal‐1inallergiclunginflammation.UsingOVAandABPAexperimentalmodelsofallergicairways,weshowedthatST6Gal‐1deficiencyledtogreaterairwayinflammationcharacterizedbyexcessiveairwayeosinophilia.TheseverityofairwayinflammationwassimilarbetweenSiat1ΔP1andSiat1nullmice,indicatingaroleforP1‐generatedST6Gal‐1inregulatingeosinophilicinflammation.Colony‐formingassayssuggestedgreaterIL‐5‐dependenteosinophilprogenitornumbersinthemarrowofST6Gal‐1‐deficientanimals.Moreover,allergenprovocationofwild‐typemiceledtoasignificantreductioninP1‐mediatedST6Gal‐1mRNAandaccompanieddeclineincirculatoryST6Gal‐1levels.Takentogether,thedataimplicateST6Gal‐1asaparticipantinregulatingnotonlyTh1butalsoTh2responses,andST6Gal‐1deficiencycanleadtothedevelopmentofmoresevereallergicinflammationwithexcessiveeosinophilproduction...

【 授权许可】

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