Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria
Procoagulant properties of microparticles released from red blood cells in paroxysmal nocturnal haemoglobinuria
复制标题
DOI：
10.1111/j.1365-2141.2010.08505.x
复制
发表时间：
2011-03-01
影响因子：
6.5
通讯作者：
Ninomiya, Haruhiko
中科院分区：
文献类型：
--
作者：
Kozuma, Yukinori;Sawahata, Yuka;Ninomiya, Haruhiko
阵发性睡眠性血红蛋白尿症（PNH）的血栓形成被认为是由几种病理生理状态引起的：纤溶系统受抑制，白细胞源性组织因子增加，补体（C '）介导的血小板和内皮细胞损伤，或血小板和内皮细胞源性微粒（MP）增加。由于溶血性发作往往伴随着血栓形成的PNH，我们研究的作用，C '-诱导的MP释放PNH的血栓形成。当通过在C '活化的PNH红细胞（RBC）存在下产生凝血酶来评估时，C'活化诱导PNH红细胞（RBC）中的促凝血改变，其通过随后用膜联蛋白V处理来消除。通过磷脂酰丝氨酸结合凝血酶原酶活性测量的显著量的促凝血MP从PNH RBC中释放，与C5 b-9的形成相关，但在C5 b-8之前不显著。还通过流式细胞术研究了来自C '活化RBC的促凝血剂、膜联蛋白V结合MP的产生。蛋白激酶C（PKC）激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯（phorbol 12-myristate 13-acetate）可诱导正常和PNH RBC释放MP，而C '诱导的PNH RBC释放MP不依赖于Ca ~（2+），与PKC、calpain或caspase的激活无关。PNH患者红细胞释放的MP具有促凝作用，可能与PNH患者的血栓形成有关。
P>Thrombosis in paroxysmal nocturnal haemoglobinuria (PNH) has been suggested to be due to several pathophysiological states: a suppressed fibrinolytic system, increased leucocyte-derived tissue factor, complement (C')-mediated damage to platelets and endothelia, or increased platelet- and endothelium-derived microparticles (MPs). Because haemolytic attack is often accompanied by thrombosis in PNH, we studied the role of C'-induced release of MPs in the thrombogenesis of PNH. C' activation induced procoagulant alteration in PNH red blood cells (RBC), when assessed by thrombin generation in the presence of C'-activated PNH RBC, which was abolished by their subsequent treatment with annexin V. Significant amounts of procoagulant MPs, measured by phosphatidylserine-binding prothrombinase activity, were released from PNH RBC in association with the formation of C5b-9, but not significantly before C5b-8. Generation of procoagulant, annexin V-binding, MPs from C'-activated RBC was studied also by flow cytometry. While phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), induced the release of MPs from normal RBC as well as PNH RBC, C'-induced release of MPs from PNH RBC was Ca2+-independent and not associated with the activation of PKC, calpain or caspase. Procoagulant properties of MPs released from PNH RBC could contribute to the thrombogenesis of PNH.