N‐Acylhomoserine lactones are potent neutrophil chemoattractants that act via calcium mobilization and actin remodeling

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

关键词: quorum sensing;    migration;    Ca2+ ;    PLC;    Rho‐;    GTPases;    cytoskeleton;   

DOI  :  10.1189/jlb.0111034

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Ingram‐negativebacteria,cell‐cellcommunicationbasedonHSLQSmoleculesisknowntocoordinatetheproductionofvirulencefactorsandbiofilms.Thesebacterialsignalscanalsomodulatehumanimmunecellbehavior.UsingaTranswellmigrationassay,wefoundthathumanprimaryneutrophilsarestronglystimulatedby3O‐C12‐HSLand‐C10‐HSLbutnotC4‐HSLinaconcentration‐dependentmanner.Moreover,3O‐C12‐HSLand‐C10‐HSLactivatePLCγ1butnot‐γ2,mobilizeintracellularcalcium,andup‐regulateIP3R.ThesechangeswereparalleledbyF‐actinaccumulation,primarilyintheleadingedgeofneutrophils,asevidencedbyphalloidinstainingandconfocalmicroscopy.F‐andG‐actinisolationandquantificationbyimmunoblottingrevealedthattheF/G‐actinratiowasincreasedsignificantlyaftertreatmentwithallthreeHSLs.Furthemore,3O‐C12‐HSL‐and3O‐C10‐HSLtreatmentresultedinphosphorylationofRac1andCdc42.Incontrast,C4‐HSLhadnegligibleinfluenceonthephosphorylationstatusofPLCandRac1/Cdc42andfailedtoattractneutrophilsandinducecalciumrelease.Thecalciuminhibitorthapsigargin,whichblocksERcalciumuptake,stronglypreventedneutrophilmigrationtoward3O‐C12‐HSLand‐C10‐HSL.ThesefindingsshowthatthebacterialQSmolecules3O‐C12‐HSLand‐C10‐HSLmayattracthumanneutrophilstothesitesofbacterialinfectionanddevelopingbiofilms.Indeed,recognitionofHSLQSsignalsbyneutrophilsmayplayacriticalroleintheirrecruitmentduringinfections...

【 授权许可】

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