Myeloid cells are tunable by a polyanionic polysaccharide derivative and co‐determine host rescue from lethal virus infection

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

关键词: neutrophils;    recruitment;    GCP‐;    2;    antiviral;    encephalomyelitis;    COAM;   

DOI  :  10.1189/jlb.1109724

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Insightintomolecularandcellularmechanismsofinnateimmunityiscriticaltounderstandviralpathogenesisandimmunopathologyandmightbeexploitedfortherapy.WhereasthemolecularmechanismsoftheIFNdefensearewellestablished,cellularmechanismsofantiviralimmunityareonlyemerging,andtheirpharmacologicaltriggeringremainsunknown.COAMisapolysaccharidederivativewithantiviralactivitybutwithoutcomprehensionaboutitsmechanismofaction.TheCOAMmixturewasfractionated,andprophylactictreatmentofmicewithCOAMpolymersofhighMWresultedinaconversionfrom100%lethalmengovirusinfectiontoanoverallsurvivalrateof93%withoutobviousclinicalsequelae.DifferentialandquantitativeanalysisofperitonealleukocytesdemonstratedthatCOAMinducedaprofoundinfluxofneutrophils.Selectivecelldepletionexperimentspointedtowardneutrophilsandmacrophagesaskeyeffectorcellsintherescueofmicefromlethalmengovirus.COAMwasabletoinducemRNAandproteinexpressionofthemouseneutrophilchemokineGCP‐2.BindingofGCP‐2toCOAMwasdemonstratedinsolutionandconfirmedbySPRtechnology.AlthoughCOAMwasnotchemotacticforneutrophils,COAM‐anchoredmuGCP‐2retainedchemotacticactivityforhumanandmouseneutrophils.Inconclusion,thisstudyestablishedthatCOAMrescuedmicefromacuteandlethalmengovirusinfectionbyrecruitingantiviralleukocytestothesiteofinfection,asproposedthroughtheinduction,binding,andconcentrationofendogenouschemokines.Thesefindingsreinforcetheroleofneutrophilsandmacrophagesascriticalcellsthatcanbemanipulatedtowardantiviraldefense...

【 授权许可】

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