Yamamoto C, Tsuru D, Oda-Ueda N, Ohno M, Hattori S, Kim S T
Faculty of Engineering, Sojo University, Ikeda, Kumamoto, Japan.
Pharmacol Toxicol. 2001 Oct;89(4):188-94. doi: 10.1111/j.0901-9928.2001.890408.x.
Trimeresurus flavoviridis (habu snake) bites can be fatal to man because of its virulent venom, which is clinicopathologically classified as haemorrhagic, necrotic, and haemolytic toxins. Trimeresurus flavoviridis venom causes lysis of human erythrocytes in conditions where plasma is present as well as in plasma-free conditions in a dose-dependent manner. The haemolytic process requires Ca2+ and Mg2+ ions in the solution. Additionally, the venom initiates activation of the human complement cascade as evidenced by C3a and C5a releases, complement consumption indicated by CH50 and formation of soluble membrane attack complex. The insertion of membrane attack complex into the erythrocyte membranes is morphologically identified by electronmicroscopy. Immunofluorescence analysis reveals that incubation of erythrocytes with the venom decreased cell-surface expression of CD55 (decay accelerating factor) and CD59 (protectin), which renders erythrocyte more vulnerable to adherent C3 and C5 convertases and to polymerization of C9 into membranes, and may enhance autologous complement-mediated haemolysis triggered by the venom. Our data demonstrate that Trimeresurus flavoviridis venom induces haemolysis in the presence of plasma by three distinct mechanisms, direct lipolysis through PLA2 activity, activation of the human complement system, and cleavages of CD55 and CD59 from erythrocyte membranes.
竹叶青蛇咬伤可致人死亡,因其毒液毒性极强,在临床病理上可分为出血性、坏死性和溶血性毒素。竹叶青蛇毒在有血浆存在以及无血浆的条件下均能以剂量依赖的方式导致人红细胞溶解。溶血过程需要溶液中的Ca2+和Mg2+离子。此外,该毒液可引发人补体级联反应的激活,C3a和C5a的释放、CH50所示的补体消耗以及可溶性膜攻击复合物的形成均证明了这一点。通过电子显微镜在形态学上可鉴定膜攻击复合物插入红细胞膜的情况。免疫荧光分析显示,红细胞与毒液孵育后,CD55(衰变加速因子)和CD59(保护素)的细胞表面表达降低,这使得红细胞更容易受到黏附的C3和C5转化酶以及C9聚合成膜的影响,并可能增强毒液引发的自身补体介导的溶血。我们的数据表明,竹叶青蛇毒通过三种不同机制在血浆存在的情况下诱导溶血,即通过磷脂酶A2活性直接进行脂解、激活人补体系统以及从红细胞膜上裂解CD55和CD59。