Leukocyte and endothelial cell adhesion molecules in a chronic murine model of myocardial reperfusion injury.
Leukocyte and endothelial cell adhesion molecules in a chronic murine model of myocardial reperfusion injury.
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DOI：
10.1152/ajpheart.2000.279.5.h2196
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发表时间：
2000-11
期刊：
影响因子：
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通讯作者：
S. P. Jones;Steven D. Trocha;M. B. Strange;D. Granger;Christopher G. Kevil;Daniel C. Bullard;D. Lefer
中科院分区：
文献类型：
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作者：
S. P. Jones;Steven D. Trocha;M. B. Strange;D. Granger;Christopher G. Kevil;Daniel C. Bullard;D. Lefer
内皮细胞和白细胞粘附分子的表达是炎症过程中多形核中性粒细胞（PMN）募集的主要决定因素。已经证明，这些分子的药理学抑制可以减弱PMN流入和随后的组织损伤。我们测定了冠状动脉闭塞后和再灌注3天内α-颗粒膜蛋白-40（P-selectin）、内皮白细胞粘附分子1（E-selectin）和细胞间粘附分子1（ICAM-1）的时间表达。所有这些细胞粘附分子的表达在再灌注24 h左右达到峰值。我们利用P-选择素、E-选择素、ICAM-1和CD 18缺陷（-/-）小鼠，测定这些分子对PMN浸润的贡献程度。各组均行冠状动脉左前降支（LAD）局部缺血30 min，再灌注24 h。使用组织学技术评估缺血-再灌注（I/R）区的PMN积聚。P-选择素、E-选择素、ICAM-1和CD 18的表达降低可明显减少PMN向I/R心肌的浸润（P < 0.05）。此外，与野生型小鼠相比，P-选择素、E-选择素、ICAM-1和CD 18-/-小鼠在MI/R后表现出显著（P < 0.05）更小的坏死面积。这些数据表明，MI/R诱导小鼠冠状动脉血管中P-选择素、E-选择素和ICAM-1的表达。此外，P-选择素、E-选择素、ICAM-1或CD 18的遗传缺陷减弱体内MI/R后的PMN隔离和心肌损伤。结论：P-选择素、E-选择素、ICAM-1和CD 18参与了小鼠心肌梗死/再灌注损伤的发病机制。
Expression of endothelial and leukocyte cell adhesion molecules is a principal determinant of polymorphonuclear neutrophil (PMN) recruitment during inflammation. It has been demonstrated that pharmacological inhibition of these molecules can attenuate PMN influx and subsequent tissue injury. We determined the temporal expression of alpha-granule membrane protein-40 (P-selectin), endothelial leukocyte adhesion molecule 1 (E-selectin), and intercellular cell adhesion molecule 1 (ICAM-1) after coronary artery occlusion and up to 3 days of reperfusion. The expression of all of these cell adhesion molecules peaked around 24 h of reperfusion. We determined the extent to which these molecules contribute to PMN infiltration by utilizing mice deficient (-/-) in P-selectin, E-selectin, ICAM-1, and CD18. Each group underwent 30 min of in vivo, regional, left anterior descending (LAD) coronary artery ischemia and 24 h of reperfusion. PMN accumulation in the ischemic-reperfused (I/R) zone was assessed using histological techniques. Deficiencies of P-selectin, E-selectin, ICAM-1, or CD18 resulted in significant (P < 0.05) attenuation of PMN infiltration into the I/R myocardium (MI/R). In addition, P-selectin, E-selectin, ICAM-1, and CD18 -/- mice exhibited significantly (P < 0.05) smaller areas of necrosis after MI/R compared with wild-type mice. These data demonstrate that MI/R induces coronary vascular expression of P-selectin, E-selectin, and ICAM-1 in mice. Furthermore, genetic deficiency of P-selectin, E-selectin, ICAM-1, or CD18 attenuates PMN sequestration and myocardial injury after in vivo MI/R. We conclude that P-selectin, E-selectin, ICAM-1, and CD18 are involved in the pathogenesis of MI/R injury in mice.