Upregulation of P-selectin and intercellular adhesion molecule-1 after retinal ischemia-reperfusion injury.

Upregulation of P-selectin and intercellular adhesion molecule-1 after retinal ischemia-reperfusion injury.
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DOI:
10.1167/iovs.02-1324
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发表时间:
2003-11
影响因子:
4.4
通讯作者:
Akiko Nishiwaki;T. Ueda;S. Ugawa;S. Shimada;Y. Ogura
Akiko Nishiwaki;T. Ueda;S. Ugawa;S. Shimada;Y. Ogura
中科院分区:
医学2区
文献类型:
--
作者:
Akiko Nishiwaki;T. Ueda;S. Ugawa;S. Shimada;Y. Ogura

文献摘要

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目的视网膜缺血后血管内皮细胞和白细胞表达多种炎性黏附受体,如选择素和细胞黏附分子。它们调节白细胞的迁移过程。为进一步了解白细胞在视网膜缺血再灌注损伤中的作用,观察了白细胞-内皮细胞黏附分子P-选择素和细胞间黏附分子-1在视网膜缺血再灌流过程中的变化。方法雄性有色大鼠结扎视神经1h后再灌流造成视网膜缺血模型。用半定量聚合酶链式反应和Western印迹分析检测再灌注后0.5、1、6、12、24小时P-选择素和ICAM-1的基因和蛋白表达。免疫组织化学方法检测表达ICAM-1的特定病变。结果P-选择素和ICAM-1mRNA在再灌流后6、12和24小时明显上调,其中P-选择素和ICAM-1的表达高峰均出现在再灌流后12小时。P-选择素蛋白在再灌注后6h逐渐升高,6h达最大值,而ICAM-1蛋白在再灌注后24h才开始升高。缺血再灌注损伤后内皮细胞ICAM-1免疫染色呈阳性。结论视网膜缺血再灌注可刺激P-选择素和ICAM-1的表达。观察视网膜血管内皮细胞间黏附分子-1的表达。视网膜缺血后P-选择素和ICAM-1表达上调,促进白细胞滚动和黏附。
PURPOSE Vascular endothelial cells and leukocytes express several inflammatory adhesion receptors, such as selectins and cell adhesion molecules, after retinal ischemia. They mediate the transmigration process of leukocytes. For further understanding of the role of leukocytes after retinal ischemia-reperfusion injury, the responses of the leukocyte-endothelial cell adhesion molecules P-selectin and intercellular adhesion molecule (ICAM)-1 during retinal ischemia and reperfusion were examined. METHODS Male pigmented rats were subjected to retinal ischemia by a 1-hour ligation of the optic nerve followed by reperfusion. Gene and protein expression of P-selectin and ICAM-1 were studied at 0.5, 1, 6, 12, and 24 hours after the onset of reperfusion with semiquantitative polymerase chain reaction and Western blot analysis. Immunohistochemical methods were used to detect specific lesions expressing ICAM-1. RESULTS Significant upregulation of P-selectin and ICAM-1 mRNA (at 6, 12, and 24 hours of reperfusion) were observed, with the expression peaks of both P-selectin and ICAM-1 mRNA occurring at 12 hours after reperfusion. P-selectin protein gradually increased and reached a maximum 6 hours after reperfusion, whereas ICAM-1 protein increased until 24 hours after reperfusion. Immunostaining with ICAM-1 antibodies was positive in endothelial cells after ischemia-reperfusion injury. CONCLUSIONS Retinal ischemia-reperfusion stimulates P-selectin and ICAM-1 expression. Endothelial ICAM-1 expression in retinal vessels was observed. Upregulation of P-selectin and ICAM-1, which contribute to leukocyte rolling and adhesion, were observed after retinal ischemia.