Distinct roles of GPVI and integrin alpha(2)beta(1) in platelet shape change and aggregation induced by different collagens.
Distinct roles of GPVI and integrin alpha(2)beta(1) in platelet shape change and aggregation induced by different collagens.
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GPVI 和整合素 α(2)β(1) 在不同胶原诱导的血小板形状变化和聚集中的不同作用。
DOI：
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发表时间：
2002
影响因子：
7.3
通讯作者：
S. Watson
中科院分区：
文献类型：
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作者：
G. Jarvis;B. Atkinson;D. Snell;S. Watson
1.已经提出各种血小板膜糖蛋白作为胶原蛋白的受体，在某些情况下作为特定胶原蛋白类型的受体。在这项研究中，我们比较了一系列胶原蛋白类型激活血小板的能力。2.牛胶原I-V型，天然马肌腱胶原纤维和胶原相关肽（CRP）都诱导血小板聚集和形状改变。3. FcRgamma链缺陷型血小板（也缺乏GPVI）的反应被消除，表明对GPVI/FcRgamma链复合物的关键依赖。4.对所有胶原的反应在CD 36缺乏的血小板中不受影响。5.与人血小板α（2）整联蛋白亚基结合的单克隆抗体（6 F1）对胶原蛋白诱导的聚集速率和程度的影响极小;然而，在加入所有胶原蛋白后，它延迟了聚集的发生。对于形状变化，6 F1消除了由I型和IV型胶原诱导的反应，基本上减弱了对II型、III型和V型胶原的反应，但仅部分抑制Horm胶原。6.同时阻断P2 Y（1）和P2 Y（12）受体和抑制环氧合酶表明，CRP可以独立于ADP和TxA（2）激活血小板;然而，对胶原的反应依赖于这些介质。7.这项研究证实了GPVI/FcR γ链复合物在一系列胶原激动剂诱导的血小板反应中的重要性，同时没有提供胶原类型特异性受体的证据。它还提供了α（2）β（1）的调节作用的证据，其意义取决于胶原蛋白的制备。
1. Various platelet membrane glycoproteins have been proposed as receptors for collagen, in some cases as receptors for specific collagen types. In this study we have compared the ability of a range of collagen types to activate platelets. 2. Bovine collagen types I-V, native equine tendon collagen fibrils and collagen-related peptide (CRP) all induced platelet aggregation and shape change. 3. Responses were abolished in FcRgamma chain-deficient platelets, which also lack GPVI, indicating a critical dependence on the GPVI/FcRgamma chain complex. 4. Responses to all collagens were unaffected in CD36-deficient platelets. 5. A monoclonal antibody (6F1) which binds to the alpha(2) integrin subunit of human platelets had a minimal effect on the rate and extent of aggregation induced by the collagens; however, it delayed the onset of aggregation following addition of all collagens. For shape change, 6F1 abolished the response induced by collagen types I and IV, substantially attenuated that to collagen types II, III and V, but only partially inhibited Horm collagen. 6. Simultaneous blockade of the P2Y(1) and P2Y(12) receptors, and inhibition of cyclo-oxygenase demonstrated that CRP can activate platelets independently of ADP and TxA(2); however, responses to the collagens were dependent on these mediators. 7. This study confirms the importance of the GPVI/FcRgamma chain complex in platelet responses induced by a range of collagen agonists, while providing no evidence for collagen type-specific receptors. It also provides evidence for a modulatory role of alpha(2)beta(1), the significance of which depends on the collagen preparation.