Grüner Sabine, Prostredna Miroslava, Schulte Valerie, Krieg Thomas, Eckes Beate, Brakebusch Cord, Nieswandt Bernhard
Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Versbacher Str 9, 97078 Würzburg, Germany.
Blood. 2003 Dec 1;102(12):4021-7. doi: 10.1182/blood-2003-05-1391. Epub 2003 Jul 31.
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/loxP-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.
血管壁完整性受损会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的黏附和聚集。血小板β1整合素在这些过程中的作用大多仍不明确。在此，我们通过活体荧光显微镜观察发现，在α2基因敲除小鼠甚至是通过Cre/loxP介导使其血小板上所有β1整合素缺失的小鼠中，受损颈动脉暴露的ECM上的血小板黏附和血栓生长并未显著改变。相比之下，抑制野生型小鼠血小板上的αIIbβ3整合素可阻止聚集体形成，并使血小板黏附减少60.0%。引人注目的是，αIIbβ3抑制在α2基因敲除小鼠中具有类似的效果，表明在缺乏功能性α2β1和αIIbβ3的情况下，其他受体介导抗剪切黏附。这些受体被确定为α5β1和/或α6β1，因为αIIbβ3抑制可消除β1基因敲除小鼠中的血小板黏附。我们得出结论，体内受损血管壁上的抗剪切血小板黏附是一个高度整合的过程，涉及多种整合素-配体相互作用，其中没有一种相互作用本身是必不可少的。
