Increased metallothionein gene expression, zinc, and zinc‐dependent resistance to apoptosis in circulating monocytes during HIV viremia

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

关键词: AIDS;    macrophages;    MT1;   

DOI  :  10.1189/jlb.0110051

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CirculatingmonocytesexhibitanapoptoticresistancephenotypeduringHIVviremiainassociationwithincreasedMTexpression.MTsareknowntoplayanimportantroleinzincmetabolismandimmunefunction.Wenowshow,inacross‐sectionalstudyusingperipheralmonocytes,thatexpressionofMT1isoformsE,G,H,andXisincreasedsignificantlyincirculatingmonocytecellsfromHIV+subjectsduringchronicviremicepisodesascomparedwithuninfectedsubjects.ThisincreaseinexpressionisalsoobservedduringacuteviremiafollowinginterruptionofsuppressiveART.CirculatingmonocytesfromHIV+donorswerealsofoundtohaveelevatedzincimportergeneZip8expressioninconjunctionwithelevatedintracellularzinclevelsincontrasttoCD4+T‐lymphocytes.InvitroHIV‐1infectionstudieswithelutriatedMDMconfirmadirectrelationbetweenHIV‐1infectionandincreasedMDMMT1(isoformG)geneexpressionandincreasedintracellularzinclevels.Adirectlinkbetweenelevatedzinclevelsandapoptosisresistancewasestablishedusingacell‐permeablezincchelatorTPEN,whichreversedapoptosisresistanceeffectivelyinmonocytesfromHIV‐infectedtolevelscomparablewithuninfectedcontrols.Takentogether,increasesinMTgeneexpressionandintracellularzinclevelsmaycontributedirectlytomaintenanceofanimmune‐activatedmonocytebymediatinganincreasedresistancetoapoptosisduringactiveHIV‐1viremia...

【 授权许可】

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