Neutrophilsrespondtobacterialinfectionbyreleasingreactiveoxygenspeciesthatkillbacteriaandbyexpressingchemokinesthatattractotherimmunecellstothesiteofinfection.ThemultisubunitenzymeNADPHoxidaseexpressedbyneutrophilsproducesreactiveoxygenspeciesrapidlyreleasedinwhatisknownastherespiratoryburst.ActivityoftheNADPHoxidaseisinducedbyfMLPreceptorligands,formylatedpeptidesfrombacteria.ThefMLPreceptorisaG-proteincoupledreceptor,FPR-1,thatactivatesMapkinasepathwaysandphospholipaseC.PhospholipaseCactivationreleasesIP3andcalcium,activatingproteinkinaseCandalsoactivatingthetranscriptionfactorNFAT,whichcontributestoactivationofchemokinegenes.OneofthecomponentsoftheNADPHoxidaseisp47phox.PKCactivationphosphorylatesp47phoxtoactivateNADPHoxidaseactivity.ActivationofMapkinasecascadesleadstoErk1/Erk2dependentp47phoxphosphorylationaswellasactivationoftheElk-1transcriptionfactorandchemokinegeneexpression.Inhibitionofp38didnotaffectp47phoxphosphorylation,indicatingthatp38isnotinvolvedinErk1/2activationoftheNADPHoxidase.Inhibitionofp38didinhibitNADPHoxidasethough,indicatingthatotherpathwayscontributetoactivationofthisenzyme.Thepathwaysinvolvedinneutrophilsactivationareimportanttounderstandinnateimmuneresponsestobacterialinfection.

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REFERENCES:DewasC,FayM,Gougerot-PocidaloMA,El-BennaJ.Themitogen-activatedproteinkinaseextracellularsignal-regulatedkinase1/2pathwayisinvolvedinformyl-methionyl-leucyl-phenylalanine-inducedp47phoxphosphorylationinhumanneutrophils.JImmunol.2000Nov1;165(9):5238-44.LianJP,CrossleyL,ZhanQ,HuangR,CofferP,TokerA,RobinsonD,BadweyJA.AntagoNISTsofcalciumfluxesandcalmodulinblockactivationofthep21-activatedproteinkinasesinneutrophils.JImmunol.2001Feb15;166(4):2643-50.