Annexin A1 modulates natural and glucocorticoid‐induced resolution of inflammation by enhancing neutrophil apoptosis

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

关键词: signaling cascade;    dexamethasone;    wortmannin;    rolipram;    Bcl‐;    2 family;   

DOI  :  10.1189/jlb.0112008

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThisstudyaimedatassessingwhetherAnxA1,adownstreammediatorfortheanti‐inflammatoryeffectsofGCs,couldaffectthefateofimmunecellsintissueexudates,usingLPS‐inducedpleurisyinBALB/cmice.AnxA1proteinexpressioninexudateswasincreasedduringnaturalresolution,asseenat48–72hpost‐LPS,aneffectaugmentedbytreatmentwithGCandassociatedwithmarkedpresenceofapoptoticneutrophilsinthepleuralexudates.ThefunctionalrelevanceofAnxA1wasdeterminedusinganeutralizingantibodyoranonspecificantagonistatFPR/ALXRs:eithertreatmentinhibitedbothspontaneousandGC‐inducedresolutionofinflammation.InjectionofAc2‐26(100μg,given4hintotheLPSresponse),anAnxA1‐activeN‐terminalpeptide,promotedactiveresolutionandaugmentedtheextentofneutrophilapoptosis.Suchaneffectwaspreventedbythepan‐caspaseinhibitorzVAD‐fmk.Mechanistically,resolutionofneutrophilicinflammationwaslinkedtocellapoptosiswithactivationofBaxandcaspase‐3andinhibitionofsurvivalpathwaysMcl‐1,ERK1/2,andNF‐κB.Thesenovelinvivodata,usingadynamicmodelofacuteinflammation,provideevidencethatAnxA1isamediatorofnaturalandGC‐inducedresolutionofinflammationwithprofoundeffectsonneutrophilapoptosis...

【 授权许可】

CC BY