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人类心脏移植早期和晚期急性排斥反应期间趋化因子和受体基因的表达

Chemokine and receptor-gene expression during early and late acute rejection episodes in human cardiac allografts.

作者信息

Fahmy Nader M, Yamani Mohamad H, Starling Randall C, Ratliff Norman B, Young James B, McCarthy Patrick M, Feng Jingyuan, Novick Andrew C, Fairchild Robert L

机构信息

The Glickman Urological Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.

出版信息

Transplantation. 2003 Jun 27;75(12):2044-7. doi: 10.1097/01.TP.0000069601.73079.94.

DOI:10.1097/01.TP.0000069601.73079.94
PMID:12829909
Abstract

BACKGROUND

The expression levels of several chemokine genes in heart allografts correlate with histologic rejection grade. Potential molecular differences between early and late rejection (grade > or =2) episodes were examined by testing chemokine and receptor-gene expression.

METHODS

Expression of inducible protein (IP)-10, monokine induced by IFN-gamma (Mig), interferon inducible-T cell alpha chemoattractant (I-TAC), regulated on activation normal T-cell expressed and secreted(RANTES), and their receptors CXCR3 and CCR5 was tested in 60 endomyocardial biopsies from 24 patients using quantitative (Taqman) real-time polymerase chain reaction (PCR). The biopsies were taken in the first 3 months or from the 9th to the 12th month following transplantation.

RESULTS

IP-10, Mig, RANTES, CXCR3, and CCR5 expression levels were increased in the later versus earlier biopsies (P< or =0.01) despite no change in histologic rejection-grade status. CONCLUSION These results demonstrate significantly increased expression of T-cell chemoattractants in heart allografts during later rejection when compared with episodes occurring shortly after transplantation. The findings suggest increased intensity of inflammation in rejection occurring at later times posttransplant that are revealed by molecular analyses of the graft.

摘要

背景

心脏同种异体移植物中几种趋化因子基因的表达水平与组织学排斥分级相关。通过检测趋化因子和受体基因表达,研究早期和晚期排斥反应(分级≥2)发作之间潜在的分子差异。

方法

使用定量(Taqman)实时聚合酶链反应(PCR)检测了24例患者60份心内膜活检组织中诱导性蛋白(IP)-10、γ干扰素诱导的单核因子(Mig)、干扰素诱导的T细胞α趋化因子(I-TAC)、活化正常T细胞表达和分泌调节因子(RANTES)及其受体CXCR3和CCR5的表达。活检组织取自移植后的前3个月或第9至12个月。

结果

尽管组织学排斥分级状态没有变化,但与早期活检相比,晚期活检中IP-10、Mig、RANTES、CXCR3和CCR5的表达水平升高(P≤0.01)。

结论

这些结果表明,与移植后不久发生的排斥反应相比,心脏同种异体移植物在晚期排斥反应期间T细胞趋化因子的表达显著增加。研究结果表明,移植后期发生的排斥反应中炎症强度增加,这通过对移植物的分子分析得以揭示。

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