Impaired function of Fanconi anemia type C‐deficient macrophages

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

关键词: inflammation;    motility;    cytoskeleton;   

DOI  :  10.1189/jlb.0811418

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

FAisageneticdisordercharacterizedbyBMfailure,developmentaldefects,andcancerpredisposition.PreviousstudiessuggestthatFApatientsexhibitalterationsinimmunologicfunction.However,itisunclearwhetherthedefectsareimmunecell‐autonomousorsecondarytoleukopeniafromevolvingBMfailure.Giventhecentralrolethatmacrophageshaveintheinnateimmuneresponse,inflammationresolution,andantigenpresentationforacquiredimmunity,weexaminedwhethermacrophagesfromFancc−/−miceexhibitimpairedfunction.PeritonealinflammationinducedbyLPSorsodiumperiodateresultedinreducedmonocyte/macrophagerecruitmentinFancc−/−micecomparedwithWTcontrols.Fancc−/−micealsohaddecreasedinflammatorymonocytesmobilizedintotheperipheralbloodafterLPStreatmentcomparedwithcontrols.Furthermore,Fancc−/−peritonealmacrophagesdisplayedcell‐autonomousdefectsinfunction,includingimpairedadhesiontoFNorendothelialcells,reducedchemoattractant‐mediatedmigration,anddecreasedphagocytosis.Moreover,dysregulatedF‐actinrearrangementwasdetectedinFancc−/−macrophagesafteradhesiontoFN,whichwasconsistentwithanobservedreductioninRhoA‐GTPlevels.Importantly,thesedatasuggestthatimpairedcytoskeletalrearrangementsinFancc−/−macrophagesmaybethecommonmechanismresponsibleforcell‐autonomousdefectsdetectedinvitro,aswellasalteredmonocyte/macrophagetraffickinginvivo...

【 授权许可】

CC BY