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1、在小鼠骨髓移植中CCR5与急性移植物抗宿主病的相【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),recruitothercellsinthegener
2、ationoforgandamage[1,2].Thisinpartisthe“cytokinestorm”thatfuelsGVHDpathogenesis[3].MultipleorgansareaffectedinacuteGVHDincludingtheskin,gut,lungs,andliver.TcontributestothegenerationandpathologyofGVHDinbothmanandmouse[4,5],emphasizingtheimportanceofmodelsthatcanreflecttheconditioningre
3、gimensusedinclinicalBMT.Chemokinesareadiversegroupofcytokinesthatmodulateimmunecelltraffickingandfunction[6,7].Duetothepropertiesofchemokines,ithasbeenpostulatedthatchemokinesmayplayaroleinGVHD.Serodyetal[8]demonstratedreducedlethalityinrecipientsofdonorTcellsfromMIP-1α-deficientmicepa
4、redtoediatedGVHDmodel.RecentreportsalsoindicatedthatblockadeofCCR5usingneutralizingantibodiescouldalsoprotectfromGVHDusingaparentintoF1GVHDmodel[9].ThisreportandanotherusingCCR5KOmiceinthesamemodelindicatedthatCCR5oncellsplayedaroleinaugmentingtheGVHDresponseandthatblockadeofthisintera
5、ctioncouldbeusedtopreventGVHD[9,10].Hoechanismunderlyingthisprotectionayplayaroleindoeinfectiousdiseasemodels[11],suggestingthatthisreceptor-ligandinteractionmayexertdiverseeffects.ThepreviousreportsassessingtheroleofCCR5expressiononGVHDusedamodelininistered.Chemokineproductionasarkedl
6、yinfluencedbyinflammatorycytokinesinducedaftertotal-bodyirradiation(TBI)[12,13].W6789esoughttoassesstheroleofCCR5ondonorcellsinmodelsimickingtheregimensusedinconventionalclinicalBMT.OurresultsdemonstratethattheabsenceofCCR5ondonorcellsresultsinasignificantincreaseinGVHDmorbiditythatthe
7、AnimalProductionArea(NCIatFrederick,Frederick,MD,USA).C57BL/6CCR5-/-mice(B6CCR5KO)tKuziel.AllrecipientsatchedfemalesandonthsofageatthetimeofBMT. Cellpreparation Bonemarrothebackbones,femurs,andtibiaeintoDulbecco′sphosphate-bufferedsalinesolution(DPBS)ortarandpestle,filteringthrough