资源描述:
《在小鼠骨髓移植中ccr5与急性移植物抗宿主病的相关性研究论文》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、在小鼠骨髓移植中CCR5与急性移植物抗宿主病的相关性研究论文【摘要】本研究评价供者CCR5在经过强化预处理的骨髓移植动物模型受者体内的作用,为今后的异基因造血干细胞移植的临床应用提供科学依据。经过致死剂量照射的BALB/c小鼠接受异基因C57BL/6小鼠的骨髓移植。根据回输的细胞不同实验分为4组:B6CCR5KO组,受者接受C57BL/6CCR5-/-小鼠骨髓和脾脏细胞;B6C组,受者只接受C57BL/6CCR5-/-小鼠骨髓细胞;B6C组,受者只接受野生型C57BL/6小鼠骨髓细胞。结果表明:较之B6Tasselves),recruitothercells
2、inthegenerationoforgandamage[1,2].Thisinpartisthe“cytokinestorm”thatfuelsGVHDpathogenesis[3].MultipleorgansareaffectedinacuteGVHDincludingtheskin,gut,lungs,andliver.TcontributestothegenerationandpathologyofGVHDinbothmanandmouse[4,5],emphasizingtheimportanceofmodelsthatcanreflectthe
3、conditioningregimensusedinclinicalBMT.Chemokinesareadiversegroupofcytokinesthatmodulateimmunecelltraffickingandfunction[6,7].Duetothepropertiesofchemokines,.freelokinesmayplayaroleinGVHD.Serodyetal[8]demonstratedreducedlethalityinrecipientsofdonorTcellsfromMIP-1α-deficientmicepared
4、toediatedGVHDmodel.RecentreportsalsoindicatedthatblockadeofCCR5usingneutralizingantibodiescouldalsoprotectfromGVHDusingaparentintoF1GVHDmodel[9].ThisreportandanotherusingCCR5KOmiceinthesamemodelindicatedthatCCR5oncellsplayedaroleinaugmentingtheGVHDresponseandthatblockadeofthisinter
5、actioncouldbeusedtopreventGVHD[9,10].Hoechanismunderlyingthisprotectionayplayaroleindoeinfectiousdiseasemodels[11],suggestingthatthisreceptor-ligandinteractionmayexertdiverseeffects.ThepreviousreportsassessingtheroleofCCR5expressiononGVHDusedamodelininistered.Chemokineproductionasa
6、rkedlyinfluencedbyinflammatorycytokinesinducedaftertotal-bodyirradiation(TBI)[12,13].T.OurresultsdemonstratethattheabsenceofCCR5ondonorcellsresultsinasignificantincreaseinGVHDmorbiditythattheAnimalProductionArea(NCIatFrederick,Frederick,MD,USA).C57BL/6CCR5-/-mice(B6CCR5KO)tKuziel.A
7、llrecipientsatchedfemalesandonthsofageatthetimeofBMT.CellpreparationBonemarrothebackbones,femurs,andtibiaeintoDulbecco′sphosphate-bufferedsalinesolution(DPBS)ortarandpestle,filteringthroughameshfiltertoremoveparticulates,andphnodecellpreparationsovedebrisandented(FBS)forinvitroassa
8、ys.CellcountsedonaCoulterZ