Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury.
Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury.
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DOI：
10.1016/j.yjmcc.2005.07.006
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发表时间：
2005-12
影响因子：
5
通讯作者：
N. Takaya;Y. Katoh;K. Iwabuchi;Ichiro Hayashi;H. Konishi;Seigo Itoh;K. Okumura;C. Ra;I. Nagaoka;H. Daida
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文献类型：
--
作者：
N. Takaya;Y. Katoh;K. Iwabuchi;Ichiro Hayashi;H. Konishi;Seigo Itoh;K. Okumura;C. Ra;I. Nagaoka;H. Daida
冠状动脉内血小板活化和微聚集体的形成在心肌缺血再灌注损伤中起着重要作用。Fc受体γ链（FcR γ）与糖蛋白（GP）VI共表达，形成血小板胶原蛋白受体，胶原蛋白对血小板的激活与FcRγ的酪氨酸磷酸化密切相关。为了研究血小板FcR γ/GPVI复合物在小鼠心肌缺血和再灌注损伤早期的功能意义，我们使用野生型小鼠和缺乏GPVI的FcRγ缺陷（FcRγ-/-）小鼠进行冠状动脉闭塞和再灌注实验。FcRγ-/-小鼠冠状动脉闭塞和再灌注的梗死面积明显小于对照FcR γ+/+小鼠。再灌注后24小时，损伤组织的电子显微镜显示野生型小鼠损伤区域毛细血管中的血小板聚集和闭塞性血小板微血栓显著多于FcR γ-/-小鼠。心肌缺血再灌注后，FcR γ-/-小鼠血小板Syk几乎没有激活，而FcR γ+/+小鼠血小板Syk明显激活。两组小鼠心肌缺血再灌注后中性粒细胞CD 11b表达均升高，而FcRγ-/-小鼠损伤区髓过氧化物酶活性显著低于FcRγ+/+小鼠。提示胶原通过FcR γ激活血小板在心肌缺血再灌注损伤中起着重要作用。FcRγ和GPVI可能是心肌缺血再灌注损伤的重要治疗靶点。
Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor γ-chain (FcR γ) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcRγ. To examine the functional significance of platelet FcR γ/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcRγ-deficient (FcRγ–/–) mice that lack GPVI. The infarct size was significantly smaller in FcRγ–/–mice subjected to occlusion and reperfusion of the coronary artery than in control FcR γ+/+mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR γ–/–mice. Platelet Syk was scarcely activated in the FcR γ–/–mice after myocardial ischemia and reperfusion, but significantly activated in the FcR γ+/+mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcRγ–/–mice than in the FcRγ+/+mice. These results suggest that the collagen-induced activation of platelets through the FcR γ plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRγ and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.