PLA2G5 regulates transglutaminase activity of human IL‐4‐activated M2 macrophages through PGE2 generation

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

关键词: inflammation;    eosinophil;    nasal polyp;    TGM2;    phospholipase A2;    asthma;   

DOI  :  10.1189/jlb.3A0815-372R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

PhospholipasesA2areenzymesthatliberatemembrane‐boundlipidsinatissueandcell‐specificfashion.GroupVsecretoryphospholipaseA2isnecessaryforthedevelopmentofM2macrophagesandtheireffectorfunctionsinamousemodeloftheT‐helper‐2allergicairwayinflammation.However,thefunctionofgroupVphospholipaseA2inhumanM2activationandT‐helper‐2inflammationisill‐defined.Transglutaminase‐2,aproteincross‐linkingenzyme,isanewlyidentifiedmarkerofbothhumanandmouseinterleukin‐4‐activatedM2macrophagesandisalsofoundinthelungsofpatientswithasthma.WereportthatgroupVphospholipaseA2andtransglutaminase‐2colocalizedinmacrophagesofhumannasalpolyptissueobtainedfrompatientswithT‐helper‐2eosinophilicinflammation,andtheircoexpressionpositivelycorrelatedwiththenumberofeosinophilsineachtissuespecimen.Wedemonstratethatinhumanmonocyte‐derivedmacrophagesactivatedbyinterleukin‐4,groupVphospholipaseA2translocatedandcolocalizedwithtransglutaminase‐2inthecytoplasmandonthemembraneofmacrophages.Moreover,knockingdowngroupVphospholipaseA2withsmallinterferingribonucleicacidreducedmacrophagetransglutaminaseactivity,whereasmassspectrometryanalysisoflipidsalsoshowedreducedprostaglandinE2production.Finally,exogenousprostaglandinE2restoredtransglutaminaseactivityofgroupVphospholipaseA2‐smallinterferingribonucleicacid–treatedmacrophages.Thus,ourstudyshowsanovelfunctionofgroupVphospholipaseA2inregulatingthetransglutaminaseactivityofhumaninterleukin‐4–activatedM2macrophagesthroughprostaglandinE2generationandsuggeststhatgroupVphospholipaseA2isafunctionallyrelevantenzymethatmayhavetherapeuticvalueforthetreatmentofhumanT‐helper‐2inflammatorydisorders...

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