Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
PLA2G5 regulates transglutaminase activity of human IL‐4‐activated M2 macrophages through PGE2 generation | |
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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