Myeloperoxidase: a front‐line defender against phagocytosed microorganisms

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

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...

【 授权许可】

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