Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo
Multiple integrin-ligand interactions synergize in shear-resistant platelet adhesion at sites of arterial injury in vivo
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DOI：
10.1182/blood-2003-05-1391
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发表时间：
2003-12-01
期刊：
影响因子：
20.3
通讯作者：
Nieswandt, B
中科院分区：
文献类型：
--
作者：
Grüner, S;Prostredna, M;Nieswandt, B
血管壁完整性受损导致内皮下细胞外基质（ECM）暴露，从而引发整合素依赖性血小板粘附和聚集。血小板 β1 整合素在这些过程中的作用大多仍不清楚。在这里，我们通过活体荧光显微镜证明，在α2缺失小鼠中，甚至在Cre/IoxP介导的血小板上所有β1整合素缺失的小鼠中，受损颈动脉暴露的ECM上的血小板粘附和血栓生长没有显着改变。相比之下，抑制野生型小鼠血小板上的 αIIbbeta3 整合素可阻止聚集体形成，并使血小板粘附减少 60.0%。引人注目的是，αIIbβ3 抑制在 α2 缺失小鼠中具有类似的效果，这表明其他受体在缺乏功能性 α2β1 和 αIIbbeta3 的情况下介导抗剪切粘附。这些被鉴定为 alpha5beta1 和/或 alpha6beta1，因为 alphaIIbbeta3 抑制消除了 beta1 缺失小鼠中的血小板粘附。我们得出的结论是，体内受损血管壁上的抗剪切血小板粘附是一个高度集成的过程，涉及多种整合素-配体相互作用，其中任何一个本身都不是必需的。 (C) 2003 年，美国血液学会。
Damage to the integrity of the vessel wall results in exposure of the subendothelial extracellular matrix (ECM), which triggers integrin-dependent adhesion and aggregation of platelets. The role of platelet beta1 integrins in these processes remains mostly undefined. Here, we demonstrate by intravital fluorescence microscopy that platelet adhesion and thrombus growth on the exposed ECM of the injured carotid artery is not significantly altered in alpha2-null mice and even in mice with a Cre/IoxP-mediated loss of all beta1 integrins on their platelets. In contrast, inhibition of alphaIIbbeta3 integrin on platelets in wild-type mice blocked aggregate formation and reduced platelet adhesion by 60.0%. Strikingly, alphaIIbbeta3 inhibition had a comparable effect in alpha2-null mice, demonstrating that other receptors mediate shear-resistant adhesion in the absence of functional alpha2beta1 and alphaIIbbeta3. These were identified to be alpha5beta1 and/or alpha6beta1 as alphaIIbbeta3 inhibition abrogated platelet adhesion in beta1-null mice. We conclude that shear-resistant platelet adhesion on the injured vessel wall in vivo is a highly integrated process involving multiple integrin-ligand interactions, none of which by itself is essential. (C) 2003 by The American Society of Hematology.