Influence of fibrillar collagen structure on the mechanisms of platelet thrombus formation under flow
Influence of fibrillar collagen structure on the mechanisms of platelet thrombus formation under flow
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DOI：
10.1182/blood.v94.8.2704.420k41_2704_2715
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发表时间：
1999-10-15
期刊：
影响因子：
20.3
通讯作者：
Ruggeri, ZM
中科院分区：
文献类型：
--
作者：
Savage, B;Ginsberg, MH;Ruggeri, ZM
我们使用实时视频显微镜来研究血小板粘附到暴露于 Rowing 血液的不同结构的 I 型胶原纤维上的机制。通过表面复制进行的电子显微镜分析表明，酸不溶性原纤维之间存在形态差异，显示出规则重复的条纹图案（带状胶原），而酸溶性原纤维则通过胃蛋白酶处理不溶性胶原产生，尺寸较小，具有螺旋结构（非带状胶原）。这些结构差异被证明与血小板整合素α（2）β（1）在各种流动条件下稳定与胶原蛋白粘附的作用有关，用单克隆抗体阻断α（2）β（1）功能对血小板与高密度包被在玻璃表面上的不溶性I型胶原蛋白的粘附没有影响，而存在绝对依赖性 α(2)β(1) 在相同条件下对血小板的初始永久停滞和随后胃蛋白酶溶解的 I 型胶原上的血栓形成发挥作用。相比之下，即使在血小板α(2)β(1)功能被阻断的情况下，由胃蛋白酶溶解的I型胶原制备的重构带状原纤维也支持血小板粘附和血栓形成，通过将该底物预先暴露于流动下的自体血浆，这一过程大大加速。这些结果表明血小板上除 α(2)β(1) 以外的胶原蛋白受体可以选择性地接合带状 I 型胶原蛋白中的结构域，但当 α(2)β(1) 功能被阻断时，该受体不能选择性地接合非带状 I 型胶原蛋白中的结构域。此外，胶原蛋白结构可以调节血浆成分（例如冯·维勒布兰德因子和/或其他α（平行于b）β（3）配体）流动下的结合程度和亲和力，（C）1999，美国血液学会。
We have used real-time video microscopy to study the mechanisms of platelet adhesion to type I collagen fibrils of distinct structure exposed to Rowing blood. Electron microscopy analysis by surface replication demonstrated morphological differences between acid-insoluble fibrils, displaying a regularly repeating striated pattern (banded collagen), and acid-soluble fibrils generated by pepsin treatment of insoluble collagen, smaller in size with a helical configuration (nonbanded collagen). These structural differences proved to be related to the role of platelet integrin alpha(2)beta(1) in stabilizing adhesion to collagen under a variety of flow conditions, Blocking alpha(2)beta(1) function with a monoclonal antibody had no effect on platelet adhesion to insoluble type I collagen coated at high density on a glass surface, whereas there was an absolute dependence of alpha(2)beta(1) function for the initial permanent arrest of platelets and subsequent thrombus formation on pepsin-solubilized type I collagen under the same conditions. In contrast, reconstituted, banded fibrils prepared from pepsin-solubilized type I collagen supported platelet adhesion and thrombus development even when platelet alpha(2)beta(1) function was blocked, a process that was greatly accelerated by pre-exposure of this substrate to autologous plasma under flow. These results Implicate a collagen receptor(s) on platelets other than alpha(2)beta(1) that can selectively engage domains in banded, but not nonbanded type I collagen when alpha(2)beta(1) function is blocked. in addition, collagen structure may regulate the extent and affinity of the binding under flow of plasma components such as von Willebrand factor and/or other alpha(parallel to b)beta(3) ligands, (C) 1999 by The American Society of Hematology.