Robust erythrophagocytosis leads to macrophage apoptosis via a hemin‐mediated redox imbalance: role in hemolytic disorders

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

关键词: red blood cell;    cell death;    hemoglobin;    phagocytosis;    reactive oxygen species;    heme oxygenase‐;    1;   

DOI  :  10.1189/jlb.0510249

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

MPfromtheRESareresponsiblefortheclearanceofsenescentRBC.AlthoughthefrequencyofsenescentRBCislowundersteady‐stateconditions,itincreasesdramaticallyduringhemolyticdisorders,resultinginenhancederythrophagocytosis.AserythrophagocytosishasbeeninvolvedinMPdysfunctionandascertainhemolyticdisordersassociatetoMPapoptosis,apossiblelinkbetweenerythrophagocytosisandtheviabilityofphagocyteswasinvestigatedherein.Tomimichemolyticdisorders,twodistinctinvitromodels,artificiallyoxidizedRBCandDSRBC,werechosentostudytheerythrophagocytosisimpactontheviabilityofJ774A.1MP.AlthoughCRBCwereweaklyphagocytosedanddidnotaffectMPviabilitysignificantly,erythrophagocytosisofoxidizedRBCandDSRBCwasrobustandresultedinasharpdecreaseofMPviabilityviaapoptosis.Undertheseconditions,Hb‐derivedHEwasshowntobeinvolvedintheinductionofapoptosis.Moreover,oxidizedRBC,DSRBC,andHEgeneratedROSspecies,whichwereresponsiblefortheapoptosisofMP.Furthermore,HO‐1,stronglyinducedinresponsetotreatmentwithoxidizedRBC,DSRBC,orHE,wasshowntoprotectMPpartiallyagainstapoptosis,suggestingthatrobusterythro‐phagocytosismayexceedthedetoxificationcapabilitiesofMP.Takentogether,theseresultssuggestthatenhancederythrophagocytosisassociatedtohemolyticdisordersleadstoMPapoptosisinvitroandmayhavecriticalimplicationsforthecontrolofmalariainfectionandfortheexacerbatedsusceptibilitytobacterialinfectionsduringhemolyticdisorders...

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