Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O).
Identification of a novel mode of complement activation on stimulated platelets mediated by properdin and C3(H2O).
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DOI：
10.4049/jimmunol.1300610
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发表时间：
2013-06-15
期刊：
影响因子：
--
通讯作者：
Ferreira VP
中科院分区：
文献类型：
--
作者：
Saggu G;Cortes C;Emch HN;Ramirez G;Worth RG;Ferreira VP
动脉粥样硬化和冠心病等慢性炎症性疾病患者体内循环的活化血小板数量增加。激活的血小板可以激活补体系统。虽然补体激活对于免疫应答和从循环中去除消耗的细胞是必不可少的，但它也有助于炎症和血栓形成，特别是在补体调节缺陷的患者中。促炎性活化的白细胞，其直接与血小板相互作用以响应血管损伤，是备解素的主要来源之一，备解素是旁路途径的正调节剂。备解素在补体激活受刺激血小板中的作用尚不清楚。在此，数据显示，在不存在C3的情况下，生理形式的人备解素在被强激动剂活化后直接与人血小板结合，并且与表面CD62P表达不成比例。当备解素在表面上并募集C3b或C3（H2O）以形成C3b、Bb或新的细胞结合的C3转化酶[C3（H2O），Bb]时，活化的血小板上的旁路途径的活化发生，所述转化酶通常仅存在于流体相中。或者，备解素可以被血小板表面上的C3（H2O）募集，促进补体活化。抑制H因子介导的细胞表面补体调节显著增加补体在具有表面备解素的活化血小板上的沉积。最后，由活化的中性粒细胞释放的备解素与活化的血小板结合。总之，这些数据表明，新的分子机制替代途径激活刺激血小板，可能有助于局部炎症部位的血管损伤和血栓形成。
Elevated numbers of activated platelets circulate in patients with chronic inflammatory diseases including atherosclerosis and coronary disease. Activated platelets can activate the complement system. Although complement activation is essential for immune responses and removal of spent cells from circulation, it also contributes to inflammation and thrombosis, especially in patients with defective complement regulation. Pro-inflammatory activated leukocytes, which interact directly with platelets in response to vascular injury, are among the main sources of properdin, a positive regulator of the alternative pathway. The role of properdin in complement activation on stimulated platelets is unknown. Here, the data show that physiological forms of human properdin bind directly to human platelets after activation by strong agonists, in the absence of C3, and non-proportionally to surface CD62P expression. Activation of the alternative pathway on activated platelets occurs when properdin is on the surface and recruits C3b or C3(H2O) to form C3b,Bb or a novel cell-bound C3 convertase [C3(H2O),Bb], which is normally present only in the fluid phase. Alternatively, properdin can be recruited by C3(H2O) on the platelet surface, promoting complement activation. Inhibition of factor H-mediated cell surface complement regulation significantly increases complement deposition on activated platelets with surface properdin. Finally, properdin released by activated neutrophils binds to activated platelets. Altogether, these data suggest novel molecular mechanisms for alternative pathway activation on stimulated platelets that may contribute to localization of inflammation at sites of vascular injury and thrombosis.
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影响因子：
5.3
作者：
Bröijersén, A;Karpe, F;Hjemdahl, P
通讯作者：
Hjemdahl, P
影响因子：
4.4
作者：
Ferreira, Viviana P.;Herbert, Andrew P.;Pangburn, Michael K.
通讯作者：
Pangburn, Michael K.
DOI：
10.1016/s0735-1097(97)00510-x
发表时间：
1998-02-01
影响因子：
24
作者：
Furman, MI;Benoit, SE;Michelson, AD
通讯作者：
Michelson, AD
影响因子：
20.3
作者：
Camous, Laurent;Roumenina, Lubka;Halbwachs-Mecarelli, Lise
通讯作者：
Halbwachs-Mecarelli, Lise
影响因子：
3.6
作者：
Bongrazio, M;Pries, AR;Zakrzewicz, A
通讯作者：
Zakrzewicz, A