In vitro におけるヘモグロビン小胞体の血小板活性化に対する影響

若本 志乃舞, 満博 藤原, 英樹 阿部, 美樹 山口, 真司 武岡, 英俊 土田, 久實 池田
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Abstract

Hemoglobin vesicles (HbV), a type of liposome-encapsulated hemoglobin (LEH), have been recently developed as an artificial oxygen carrier. The efficacy of HbV has been demonstrated in the transfusion of HbV into rodent models of hemorrhagic shock. It is important to evaluate the compatibility of HbV with human blood cells. We examined the effects of HbV on human platelet activation in vitro by estimating the platelet release reaction and expression of platelet surface activation markers in the presence or absence of agonists. HbV concentration in the reaction volume was prepared at 20% or 40%. Preincubation of platelet-rich plasma (PRP) with HbV had no adverse effects on RANTES or serotonin release from platelets. Preincubation of whole blood with HbV also had no effects on exposure of P-selectin on platelets. However, binding of PAC-1, a monoclonal antibody that detects the activation-dependent conformational change of αIIbβ3 to platelets, was amplified by preincubation of whole blood with HbV in the presence of relatively low concentration of ADP. These results suggest that HbV enhances the binding of PAC-1 to platelets. The clinical meaning of this increased binding of PAC-1 needs to be addressed.
对体外血红蛋白内质网血小板活化的影响
血红蛋白囊泡(HbV)是一种脂质体包裹的血红蛋白(LEH),是近年来发展起来的一种人工氧载体。乙型肝炎病毒的疗效已在输注乙型肝炎病毒到失血性休克的啮齿动物模型中得到证实。评价HbV与人血细胞的相容性是很重要的。我们通过估计在存在或不存在激动剂的情况下血小板释放反应和血小板表面活化标记物的表达,研究了HbV对体外人血小板活化的影响。反应体积中HbV浓度分别为20%或40%。富血小板血浆(PRP)与HbV预孵育对RANTES或血小板血清素释放无不良影响。全血HbV预孵育对p -选择素对血小板的暴露也没有影响。然而,PAC-1(一种检测α ib β3激活依赖性构象变化的单克隆抗体)与血小板的结合在相对低浓度ADP存在的全血中被扩增。这些结果表明HbV增强了PAC-1与血小板的结合。这种PAC-1结合增加的临床意义需要解决。
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