资源描述：
《ccl exhibits a regulatory role through inhibition of receptor and glycosaminoglycan binding》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。
1、CCL18ExhibitsaRegulatoryRolethroughInhibitionofReceptorandGlycosaminoglycanBindingSonjaC.Krohn,PaulineBonvin,AmandaE.I.Proudfoot¤a*DepartmentofImmunology,MerckSeronoGenevaResearchCentre,Geneva,SwitzerlandAbstractCCL18hasbeenreportedtobepresentconstitutivelyathigh
2、levelsinthecirculation,andisfurtherelevatedduringinflammatorydiseases.Sinceitisaratherpoorchemoattractant,wewonderedifitmayhavearegulatoryrole.CCL18hasbeenreportedtoinhibitcellularrecruitmentmediatedbyCCR3,andwehaveshownthatwhilstitisacompetitivefunctionalantagon
3、istasassessedbySchildplotanalysis,itonlybindstoasubsetofCCR3receptorpopulations.WehaveextendedthisinhibitoryactivitytootherreceptorsandhaveshownthatCCL18isabletoinhibitCCR1,CCR2,CCR4andCCR5mediatedchemotaxis,buthasnoeffectonCCR7andCCR9,northeCXCreceptorsthatwehav
4、etested.WhilstCCL18isabletobindtoCCR3,itdoesnotbindtotheotherreceptorsthatitinhibits.Wethereforetestedthehypothesisthatitmaydisplaceglycosaminoglycan(GAG)chemokinesboundeitherincis-ontheleukocyte,orintrans-presentationontheendothelialsurface,therebyinhibitingther
5、ecruitmentofleukocytesintothesiteofinflammation.WeshowthatCCL18selectivitydisplacesheparinboundchemokines,andthatchemokinesfromallfourchemokinesub-classesdisplacecellboundCCL18.WeproposethatCCL18hasregulatorypropertiesinhibitingchemokinefunctionwhenGAG-mediatedpr
6、esentationplaysaroleinreceptoractivation.Citation:KrohnSC,BonvinP,ProudfootAEI(2013)CCL18ExhibitsaRegulatoryRolethroughInhibitionofReceptorandGlycosaminoglycanBinding.PLoSONE8(8):e72321.doi:10.1371/journal.pone.0072321Editor:NathalieSignoret,UniversityofYork,Unit
7、edKingdomReceivedApril25,2013;AcceptedJuly9,2013;PublishedAugust12,2013Copyright:©2013Krohnetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedth
8、eoriginalauthorandsourcearecredited.Funding:TheresearchleadingtotheseresultshasreceivedfundingfromtheEuropeanCommunity'sSeventhFrameworkProgrammeTIMER[FP7-2007
