Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
Myeloperoxidase: a front‐line defender against phagocytosed microorganisms | |
关键词: innate immunity; host defense; phagosomes; neutrophils; | |
DOI : 10.1189/jlb.0712349 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
Successfulimmunedefenserequiresintegrationofmultipleeffectorsystemstomatchthediversevirulencepropertiesthatmembersofthemicrobialworldmightexpressastheyinitiateandpromoteinfection.Humanneutrophils—thefirstcellularresponderstoinvadingmicrobes—exertmostoftheirantimicrobialactivityinphagosomes,specializedmembrane‐boundintracellularcompartmentsformedbyingestionofmicroorganisms.ThetoxinsgenerateddenovobythephagocyteNADPHoxidaseanddeliveredbyfusionofneutrophilgranuleswithnascentphagosomescreateconditionsthatkillanddegradeingestedmicrobes.Antimicrobialactivityreflectsmultipleandcomplexsynergiesamongthephagosomalcontents,andoptimalactionreliesonoxidantsgeneratedinthepresenceofMPO.Theabsenceoflife‐threateninginfectiouscomplicationsinindividualswithMPOdeficiencyisfrequentlyofferedasevidencethattheMPOoxidantsystemisancillaryratherthanessentialforneutrophil‐mediatedantimicrobialactivity.However,thatargumentfailstoconsiderobservationsfromhumansandKOmicethatdemonstratethatmicrobialkillingbyMPO‐deficientcellsislessefficientthanthatofnormalneutrophils.WepresentevidenceinsupportofMPOasamajorarmofoxidativekillingbyneutrophilsandproposethattheessentialcontributionofMPOtonormalinnatehostdefenseismanifestonlywhenexposuretopathogensoverwhelmsthecapacityofotherhostdefensemechanisms...
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