Inhibition of complement‐mediated haemolysis in paroxysmal nocturnal haemoglobinuria by heparin or low‐molecular weight heparin
Inhibition of complement‐mediated haemolysis in paroxysmal nocturnal haemoglobinuria by heparin or low‐molecular weight heparin
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肝素或低分子肝素抑制阵发性睡眠性血红蛋白尿中补体介导的溶血
DOI：
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发表时间：
2000
影响因子：
6.5
通讯作者：
T. Nagasawa
中科院分区：
文献类型：
--
作者：
H. Ninomiya;Y. Kawashima;T. Nagasawa
阵发性睡眠性血红蛋白尿症 (PNH) 中补体 (C') 介导的溶血主要是由于受 PNH 影响的红细胞 (RBC) 中缺乏具有 C' 调节活性的糖基磷脂酰肌醇锚定膜蛋白 CD55 和 CD59。 C5b-7 疏水插入红细胞膜，启动膜攻击复合物的形成，由于 CD59 的缺乏，很容易导致 PNH 红细胞裂解。我们研究了 C5b-7 插入之前 C5b-6 和红细胞膜之间静电相互作用的重要性。在体外，C'介导的PNH红细胞裂解（通过蔗糖溶血测定评估）被肝素、低分子量肝素（LMWH）或鱼精蛋白抑制，表明C'成分和红细胞膜之间的静电相互作用在C'介导的溶血过程中的重要性。神经氨酸酶处理的 PNH 红细胞对 C' 激活产生抵抗，表明红细胞膜上的唾液酸部分参与了红细胞与 C' 成分的相互作用。通过使用生物素标记的 C7，我们证明 LMWH 和肝素抑制 C5b-7 插入红细胞，尽管它们没有抑制 C7 掺入膜相关的 C5b-6。即使在完全抑制溶血的浓度下，肝素和 LMWH 都不能抑制由 C' 激活引起的 PNH RBC 膜的促凝血改变。由于 LMWH 在体外抑制 C' 介导的 PNH 红细胞溶解，其范围可导致正常血浆的活化部分凝血活酶时间有限延长，因此我们认为 LMWH 可能有助于抑制溶血和预防血栓形成，血栓形成通常发生在 PNH 溶血发作后。
Complement (C′)‐mediated haemolysis in paroxysmal nocturnal haemoglobinuria (PNH) is mainly due to the deficiency of glycosyl phosphatidylinositol‐anchored membrane proteins with C′‐regulatory activities CD55 and CD59 in PNH‐affected red blood cells (RBCs). Hydrophobic insertion of C5b‐7 to RBC membranes, initiating the formation of a membrane attack complex, readily results in lysis of PNH RBCs due to the deficiency of CD59. We studied the significance of the electrostatic interactions between C5b‐6 and RBC membranes preceding the insertion of C5b‐7. In vitro, C′‐mediated lysis of PNH RBCs (assessed by sucrose haemolytic assay) was inhibited by heparin, low‐molecular weight heparin (LMWH) or protamine, indicating the significance of the electrostatic interactions between C′ components and RBC membranes in the process of C′‐mediated haemolysis. Neuraminidase‐treated PNH RBCs became resistant to C′ activation, suggesting that the sialic acid moieties on RBC membranes are involved in the interactions of RBC with C′ components. By using biotin‐labelled C7, we demonstrated that LMWH as well as heparin inhibited the insertion of C5b‐7 to RBCs, although they did not inhibit the incorporation of C7 into membrane‐associated C5b‐6. Neither heparin nor LMWH could inhibit the procoagulant alteration of PNH RBC membranes induced by C′ activation even at concentrations which inhibited the haemolysis completely. Because LMWH inhibited the C′‐mediated lysis of PNH RBCs in vitro at the range which induced a limited prolongation of activated partial thromboplastin time of normal plasma, we consider that LMWH may be useful for both the inhibition of haemolysis and the prevention of thrombosis, which often follow a haemolytic attack in PNH.
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影响因子：
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作者：
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DOI：
--
发表时间：
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期刊：
Journal of immunology (Baltimore, Md. : 1950)
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