Selective chemokine and receptor gene expressions in allografts that develop transplant vasculopathy
Selective chemokine and receptor gene expressions in allografts that develop transplant vasculopathy
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DOI：
10.1016/s1053-2498(02)00443-6
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发表时间：
2002-10-01
影响因子：
8.9
通讯作者：
Matsuda, H
中科院分区：
文献类型：
--
作者：
Horiguchi, K;Kitagawa-Sakakida, S;Matsuda, H
背景：趋化因子系统可能在移植血管病变中起一定作用，但目前尚未对趋化因子及其受体在移植血管病变中的表达进行全面的研究。方法：采用基于荧光的实时逆转录聚合酶链式反应技术，定量检测已知核苷酸序列的所有大鼠趋化因子及其受体基因的表达，并用免疫组织化学方法检测选定的细胞因子-受体对。结果：在所检测的13个受体基因中，CXCR3、CCR5和CCR2基因及其相应的配体基因在发生移植血管病变的移植物中被选择性和强烈地诱导。受体在心脏和主动脉移植物中的表达模式相似，尽管它们在移植物中的诱导和绝对表达水平在移植物中被放大了几倍。这些基因在形态改变变得明显之前就被诱导，并在整个新生内膜形成过程中持续表达。有趣的是，CXCR3的免疫组织化学染色显示出一种独特的表达模式：我们发现在新生内膜和外膜的外层细胞上有微弱的表达，而在新生内膜最内层的细胞上表达最强。本研究提示趋化因子受体对IP10-CXCR3、RANTES-CCR5和MCP1-CCR2在大鼠移植血管病变模型中的诊断和潜在的功能作用。
Background: Chemokine systems probably play a role in transplant vasculopathy; however, a comprehensive study of the expression of chemokines and their receptors in this disease has not been performed.Methods: The expression of all the rat chemokines and chemokine receptor genes for which the nucleotide sequences are known were quantitatively monitored using the fluorescence-based real-time reverse-transcriptase polymerase chain reaction technique, and selected cytokine-receptor pairs were determined using immunohistochemical staining. The analysis covered the whole time course of transplant vasculopathy in 2 different graft models (cardiac and aortic grafts) with 4 different strain combinations of rats.Results: Among the 13 receptor genes examined, the CXCR3, CCR5, and CCR2 genes and those of their corresponding ligands were selectively and strongly induced in grafts that develop transplant vasculopathy. The expression patterns of the receptors were similar in both cardiac and aortic allografts, although their induction and their absolute levels of expression were amplified several fold in the grafted aorta compared with heart grafts. The genes were induced before morphologic changes became apparent and expression was sustained during the whole period of neointimal formation. Interestingly, immunohistochemical staining for CXCR3 showed a unique pattern of expression: we found weak expression on cells in the outer layer of the neointima and adventitia and found the strongest staining in the innermost layer of the neointima.Conclusions:. This study suggested diagnostic as well as potential functional roles of the -chemokine-receptor pairs IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2 in rat models of transplant vasculopathy.