Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability.
Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability.
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DOI：
10.1111/j.1538-7836.2011.04488.x
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Wolberg AS
中科院分区：
文献类型：
--
作者：
Aleman MM;Gardiner C;Harrison P;Wolberg AS
微粒子(MPS)是由活化或凋亡的细胞，包括血小板和单核细胞所释放的亚微米小泡。循环中的MPS增多与血栓形成有关，然而，它们在血栓形成中的作用却知之甚少。确定MPS如何促进凝血酶的生成和调节纤维蛋白的密度和稳定性。血小板和单核细胞均取自健康供者。用钙离子载体、凝血酶受体激动肽(TRAP)或TRAP/惊厥毒素刺激血小板。用脂多糖刺激单核细胞和人单核细胞THP-1细胞。分离MPS，高速离心法洗涤，通过透射电子显微镜、纳米颗粒跟踪分析、流式细胞术、组织因子(TF)活性、凝血酶原酶活性、凝血酶生成、凝块形成、密度和稳定性进行评估。来自单核细胞(M-MPS)和血小板(PMPs)的MPS具有相似的形状和直径(100-300 nm)。M-MPS具有Tf活性(16.7±2.4 pm Tf/106MP)，支持凝血酶原酶活性，触发凝血酶生成延迟时间短于缓冲液对照组(分别为5.4±0.5和84.2±4.8分钟)。与对照组相比，M-MPS支持更快的纤维蛋白形成(分别为0.24±0.24和76.7±15.1MoD/min)，纤维蛋白网络密度增加38%，以及更高的凝血稳定性(在有组织纤溶酶原激活剂存在的情况下，浊度增加3.8倍)。相反，PMPs不具有转铁蛋白活性，支持的凝血酶原酶活性比M-MPS低2.8倍。PMPS支持接触性凝血酶的产生，但不独立地增加纤维蛋白网络的密度或稳定性。有趣的是，当与THP-1来源的MPS混合时，PMPs增加了凝血酶生成和纤维蛋白形成的速率(分别是1.7倍和1.3倍)。来自血小板和单核细胞的MPS对血栓的形成、结构和稳定性有不同的调节作用，提示对血栓形成有独特的贡献。
Microparticles (MPs) are submicron vesicles shed by activated or apoptotic cells, including platelets and monocytes. Increased circulating MPs are associated with thrombosis; however, their role in thrombogenesis is poorly understood. To determine how MPs promote thrombin generation and modulate fibrin density and stability. Platelets and monocytes were isolated from healthy donors. Platelets were stimulated with calcium ionophore, thrombin receptor agonist peptide (TRAP), or TRAP/convulxin. Monocytes and human monocytic THP-1 cells were stimulated with lipopolysaccharide. MPs were isolated, washed by high-speed centrifugation, and assessed by transmission electron microscopy, nanoparticle tracking analysis, flow cytometry, tissue factor (TF) activity, prothrombinase activity, thrombin generation, and clot formation, density, and stability. MPs from monocytes (M-MPs) and platelets (PMPs) had similar shapes and diameters (100–300 nm). M-MPs had TF activity (16.7±2.4 pM TF/106 MP), supported prothrombinase activity, and triggered shorter thrombin generation lag times than buffer controls (5.4±0.5 versus 84.2±4.8 min, respectively). Compared to controls, M-MPs supported faster fibrin formation (0.24±0.24 versus 76.7±15.1 mOD/min, respectively), 38% higher fibrin network density, and higher clot stability (3.8-fold higher turbidity in the presence of tissue plasminogen activator). In contrast, PMPs did not have TF activity and supported 2.8-fold lower prothrombinase activity than M-MPs. PMPs supported contact-dependent thrombin generation, but did not independently increase fibrin network density or stability. Interestingly, PMPs increased rates of thrombin generation and fibrin formation (1.7- and 1.3-fold, respectively) when mixed with THP-1-derived MPs. MPs from platelets and monocytes differentially modulate clot formation, structure and stability, suggesting unique contributions to thrombosis.
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