腺病毒介导mc148基因对β趋化因子的拮抗作用的的研究

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1、五、重组腺病毒Ad．MCl48在体内转染后可明显延长移植皮肤存活时间。供体皮肤局部转染后移植的存活时间为15．04-2．Od，与对照组(8．5±3．4)比较差异显著，与全身转染组比较无差别(p>o．05)。受体腹腔注射全身转染的移植皮肤存活时间分别为21．2±4．Id(只注射一次)和26．2±4．5d(注射两次)，二者差别显著(p<0．05)。六、MCl48基因可以拮抗13趋化因子，从而抑制白细胞的趋化和募集，这可能是转染后抑制皮肤移植排斥反应的原因。本研究将为MCl48基因进、／一步应用于基因治疗

2、奠定基础。yL，?关键词：趋化因子；腺病毒载体；＼一器官移植；基因克隆V111免疫排斥反应Adenovirus—mediatedgenetransferofMCl48toblockBchemokinesAbstractBackgroundTherecruitmentandactivationandentrytograftofrecipientleukocytesinresponsetoatransplantedorganconsititutetheinitialstepsofacompleximmu

3、nereactionwithoxygenradicalsandlyticenzymesreleased，whichultimatelyculminatesplayacentralroleinthisprocess．ChemokinesconsistofalargesubfamiliesofCXC(a)、CC(B)、inrejectionofthegraft．ChemokinesfamilyofcytokineswithfottrmajorCX3C(Y)andC．ChemokinebindtoGpro

4、teincoupledmemberreceptors．Chemokineswereconsideredaspotentialtargetsforimmunomodulationandinhibitingimmunerejection，iftheirbindingstoreceptorswereblocked．However，about50humanchemokinesandnearly20receptorshavebeenidentifiedandcharacterizedatpresent．Mul

5、tiplechemokinesareusuallyinducedatinflammatorysitesandmanydifferentchemokinereceptorscanbeexpressedbyasingletypeofcell．Itisdifficulttoinhibitinflammatoryreponsesbyantagonizingasinglechemokineoritsrec印for．Molluscumcontagiosumvirus(MCV)，amemberofthepoxvi

6、rusfamily，theMCl48ORFofwhichencodingachemokinehomologMCl48Pconsistingof104aminoacids．MC148PcanbindtochemokinereceptorsCCR1、CCR2、CCR5、CCR8、CXCRl、CXCR2andCXCR4andinhibittheattractionofmultipleleukocytesubjectstoQ、Bchemokines．MCl48Pantagonizechemokinesthe

7、mostbroadlytothisday．Inthepresentstudy．adenovirus—mediatedgenetransferofMC148wasperformedbothinvivoandin1titrotoantagonizechemokines，whichwasIIIhypothesizedtoinhibittherecruitmentofleukocytetograftandtoprevent，tosomeextent，immunerejection．Thisstudymigh

8、tprovideanovelwaytocontroltheimmuneresponse．Methods：1．MCl48wasamplifiedfromDNAofMCVisolatesandsequenced．TheproductwasexcisedbyBamHIandEcoRIandthenclonedintothecloningvectorpUCl9．TheclonedMCl48wassequencedagain．2．Theclonedinsertwasexcise