Superoxide mediates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules
Superoxide mediates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules
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DOI：
10.1152/ajpheart.00311.2002
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发表时间：
2003-02-01
影响因子：
4.8
通讯作者：
Granger, DN
中科院分区：
文献类型：
--
作者：
Cerwinka, WH;Cooper, D;Granger, DN
血小板参与了动脉粥样硬化、脓毒症和缺血再灌注损伤等多种血管系统疾病的发病过程，但对调节循环中的血小板和血管壁之间的相互作用的因素知之甚少。本研究的目的是明确超氧化物在脂多糖诱导的小鼠肠道小静脉血小板-内皮细胞(P/E)黏附中的作用。用活体荧光显微镜观察罗丹明-6G标记的小鼠血小板的粘附性。在对照组[野生型(WT)]小鼠注射脂多糖4小时后，检测到P/E粘附性增加了近10倍。这种反应不是由内毒素诱导的血小板激活引起的。在NAD(P)H氧化酶缺陷小鼠和中性粒细胞减少的WT小鼠中，内毒素诱导的P/E黏附显著减弱，而在接受CD18封闭单抗或CD18缺陷小鼠的WT小鼠中，这一反应不发生变化。表现细胞外超氧化物歧化酶结合特性的嵌合形式的锰超氧化物歧化酶也减弱了内毒素诱导的WT小鼠的反应。这些结果表明，中性粒细胞衍生的超氧化物在内毒素诱导的肺/肺黏附的调节中起主要作用。
Platelets have been implicated in the pathogenesis of different diseases of the vascular system, including atherosclerosis, sepsis, and ischemia-reperfusion injury; however, relatively little is known about the factors that regulate the interactions between circulating platelets and the vessel wall. The objective of this study was to define the contribution of superoxide to LPS-induced platelet-endothelial cell (P/E) adhesion in murine intestinal venules. The adhesion of rhodamine-6G-labeled murine platelets was monitored by intravital fluorescence microscopy. Four hours after LPS administration in control [wild-type (WT)] mice, an similar to10-fold increase in P/E adhesion was detected. This response did not result from LPS-induced platelet activation. The LPS-induced P/E adhesion was greatly attenuated in NAD(P)H oxidase-deficient mice and in WT mice rendered neutropenic with anti-neutrophil serum, whereas the response was unchanged in WT mice receiving a CD18 blocking MAb or in CD18-deficient mice. A chimeric form of MnSOD that exhibits the binding properties of extracellular SOD also attenuated the LPS-induced response in WT mice. These findings indicate that neutrophil-derived superoxide plays a major role in the modulation of endotoxin-induced P/E adhesion.