Pivotal Advance: The pattern recognition receptor ligands lipopolysaccharide and polyinosine‐polycytidylic acid stimulate factor B synthesis by the macrophage through distinct but overlapping mechanisms

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

关键词: Toll‐;    like receptors;    complement;    inflammation;   

DOI  :  10.1189/jlb.0809588

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TLRsandcomplementarecriticaltothehostresponseinsepsis,trauma,andischemia/reperfusion.WehypothesizethatTLRstimulationleadstosynthesisandreleaseofcomplementcomponentsbymacrophages,animportantsourceofextrahepaticcomplement.RAW264.7macrophagesorperitonealmacrophagesfromWTandTLR4‐,TLR3‐,TRIF‐,orMyD88‐deficientmicewereculturedunderstandardconditions.Insomeexperiments,cellswerepretreatedwithinhibitorsofMAPKsoraNF‐κBinhibitor.CellswerestimulatedwithTLRligandsatknownstimulatoryconcentrations.Intratrachealandi.p.injectionswerealsoperformedinmice.RT‐PCR,Westernblotting,andimmunocytochemistrywereusedforanalysis.UsingaRT‐PCR‐basedpanel,wedemonstratethatof18complementcomponentstested,factorBofthealternativepathwayisthemostrobustlyup‐regulatedcomplementcomponentinmacrophagesinresponsetoLPS.Thisup‐regulationresultsinreleaseoffactorBintothemedia.Up‐regulationoffactorBbyLPSisdependentonTLR4,TRIF,JNK,andNF‐κB.AscreenofotherTLRligandsdemonstratedthatstimulationwithpolyI:C(dsRNAanalog)alsoresultsinup‐regulationoffactorB,whichisdependentonJNKandNF‐κBbutindependentofTLR3andTRIF.Up‐regulationoffactorBisalsoobservedafterintratrachealandi.p.injectionofLPSorpolyI:Cinvivo.PRRstimulationprofoundlyinfluencesproductionandreleaseoffactorBbymacrophages.UnderstandingthemechanismsofPRR‐mediatedcomplementproductionmayleadtostrategiesaimedatpreventingtissuedamageindiversesettings,includingsepsis,trauma,andischemia/reperfusion...

【 授权许可】

CC BY