Effect of Soluble ICAM-1 on a Sj？grens Syndrome-like Phenotype in NOD Mice Is Disease Stage Dependent 英文参考文献.docVIP

下载本文档

2
0
约3.56万字
约 9页
2017-05-11 发布于上海
举报
版权申诉

Effect of Soluble ICAM-1 on a Sj？grens Syndrome-like Phenotype in NOD Mice Is Disease Stage Dependent 英文参考文献.doc

1、本文档共9页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Effect of Soluble ICAM-1 on a Sj？grens Syndrome-like Phenotype in NOD Mice Is Disease Stage Dependent 英文参考文献

EffectofSolubleICAM-1onaSjo¨gren’sSyndrome-like PhenotypeinNODMiceIsDiseaseStageDependent NienkeRoescher1,2.,JelleL.Vosters1,2,HongenYin2,GaborG.Illei2,PaulP.Tak1,JohnA.Chiorini2* 1Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 2Molecular Physiology and TherapeuticsBranch,NationalInstituteofDentalandCraniofacialResearch,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Abstract Introduction: Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. MembraneboundICAM-1isoverexpressedinthesalivaryglands(SG)ofSjo¨gren’ssyndrome(SS)patientsandhastherefore beenproposedasapotentialtherapeutictarget.TotesttheutilityofICAM-1asatherapeutictarget,weusedlocalgene therapy in Non ObeseDiabetic (NOD) mice to express soluble (s)ICAM-1 to compete with membrane bound ICAM-1 for bindingwithitsreceptor.TherapywasgivenpriortoandjustaftertheinfluxofimmunecellsintotheSG. Methods:Arecombinantserotype2adenoassociatedvirus(rAAV2)encodingICAM-1/Fcwasconstructedanditsefficacy testedinthefemaleNODmiceafterretrogradeinstillationinSGateight(earlytreatment)andten(latetreatment)weeksof age.SGinflammationwasevaluatedbyfocusscoreandimmunohistochemicalquantificationofinfiltratingcelltypes.Serum andSGtissuewereanalyzedforimmunoglobulins(Ig). Results:EarlytreatmentwithICAM-1/FcresultedindecreasedaveragenumberofinflammatoryfociwithoutchangesinT andBcellcomposition.Incontrast,latetreatedmicedidnotshowanychangeinfocusscores,butimmunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreasedIgMwithintheSGs,whereaslatetreatedmicehadincreasedIgMlevels,andonaveragehigherIgGandIgA. Conclusions:BlockingtheICAM-1/LFA-1interactionwithsICAM-1/FcmayresultinworseningofaSSlikephenotypewhen infiltrateshavealreadyformedwithintheSG.AsatreatmentforhumanSS,cautionshouldbetakentargetingtheICAM-1 axissin