Dynamics of GPIIb/IIIa-mediated platelet-platelet interactions in platelet adhesion/thrombus formation on collagen in vitro as revealed by videomicroscopy
Dynamics of GPIIb/IIIa-mediated platelet-platelet interactions in platelet adhesion/thrombus formation on collagen in vitro as revealed by videomicroscopy
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DOI：
10.1182/blood.v101.3.929
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发表时间：
2003-02-01
期刊：
影响因子：
20.3
通讯作者：
Coller, BS
中科院分区：
文献类型：
--
作者：
Patel, D;Väänänen, H;Coller, BS
在体外，基于一系列静态测量，对血小板与胶原涂层表面相互作用的传统描述是，血小板首先黏附和铺展形成单分子层，然后招募额外的血小板层。为了获得动态信息，我们在22℃下用视频相差显微镜研究了重力驱动的血小板在纯化的1型胶原上的体外沉积。与未经处理的人和野生型小鼠血小板一样，最初黏附后不久即有少量的“先锋”血小板，“跟随者”血小板附着在散布的先锋血小板上。随后，跟随者血小板附着并扩散到附近的胶原蛋白或先锋血小板上。因此，血栓的形成是一个协调的过程，而不是连续的过程。用单抗7E3(抗GPIIb/IIIa(AlphaIIbbeta3)+AlphaVbeta3)或替罗非班(抗GPIIb/IIIa)处理人血小板，不能阻止血小板黏附，但几乎消除了跟随血小板在先锋血小板和血小板血栓上的沉积。Glanzmann血小板减少症也得到了类似的结果。野生型小鼠的血小板在单抗1B5(抗GPIIb/IIIa)的存在下，以及来自Beta3缺失的小鼠的血小板在7E3或替罗非班的存在下表现出与人的血小板相似的行为。在泊松模型下，未经处理的人和野生型小鼠血小板的沉积模式符合随机分布，但用7E3和替罗非班处理的人血小板、1B5处理的小鼠血小板或Beta3缺失的血小板获得的沉积模式比预测的更均匀。因此，在这个模型系统中，GPIIb/IIIa受体的缺失或阻断会干扰血栓的形成，并改变血小板沉积的模式。(C)2003年，由美国血液病学会提供。
The conventional description of platelet interactions with collagen-coated surfaces in vitro, based on serial static measurements, is that platelets first adhere and spread to form it monolayer and then recruit additional layers of platelets. To obtain dynamic information, we studied gravity-driven platelet deposition in vitro on purified type 1 collagen by video phase-contrast microscopy at 22degreesC. With untreated human and wild-type mouse platelets, soon after the initial adhesion of a small number of "vanguard" platelets, "follower" platelets attached to the spread-out vanguard platelets. Follower platelets then adhered to and spread onto nearby collagen or over the vanguard platelets. Thus, thrombi formed as a concerted process rather than as sequential processes. Treatment of human platelets with monoclonal antibody (mAb) 7E3 (anti-GPIIb/IIIa (alphaIIbbeta3) + alphaVbeta3) or tirofiban (anti-GPIIb/IIIa) did not prevent platelet adhesion but nearly eliminated the deposition of follower platelets onto vanguard platelets and platelet thrombi. Similar results were obtained with Glanzmann thrombasthenia platelets. Wild-type mouse platelets in the presence of mAb 1B5 (anti-GPIIb/IIIa) and platelets from beta3-null mice behaved like human platelets in the presence of 7E3 or tirofiban. Deposition patterns of untreated human and wildtype mouse platelets were consistent with random distributions under a Poisson model, but those obtained with 7E3- and tirofiban-treated human platelets, 1B5-treated mouse platelets, or beta3-null platelets demonstrated a more uniform deposition than predicted. Thus, in this model system, absence or blockade of GPIIb/IIIa receptors interferes with thrombus formation and alters the pattern of platelet deposition. (C) 2003 by The American Society of Hematology.