Paroxysmal nocturnal hemoglobinuria: deficiency in factor H-like functions of the abnormal erythrocytes.
Paroxysmal nocturnal hemoglobinuria: deficiency in factor H-like functions of the abnormal erythrocytes.
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DOI：
10.1084/jem.157.6.1971
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发表时间：
1983-06-01
期刊：
影响因子：
--
通讯作者：
Müller-Eberhard HJ
中科院分区：
文献类型：
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作者：
Pangburn MK;Schreiber RD;Trombold JS;Müller-Eberhard HJ
阵发性睡眠性血红蛋白尿症（PNH）患者的红细胞含有一个亚群，该亚群缺乏正常人红细胞上存在的膜相关H因子样活性。使用液相C3转化酶实现C3b在红细胞上的初始沉积。然后用荧光素标记的C3和细胞结合的C3转化酶处理细胞。利用荧光激活细胞分选仪的分析揭示了两个不同的细胞群，其中一个是高度荧光的，表明每个细胞中有大量的C3b分子。只有这一人群（43%）在C3b沉积前暴露于酸化血清时易发生裂解（44%）。荧光较少的群体类似于正常人红细胞，并且不受酸化血清先前处理的影响。由于C3b沉积几乎完全发生在PNH红细胞群中的补体敏感细胞上，因此可以在不进行事先分离的情况下检查这些细胞的H因子样调节活性。这些功能包括通过因子I增强红细胞结合的C3 b的失活和加速红细胞结合的C3转化酶C3b，Bb的衰变。结果发现，PNH红细胞上的C3b比正常人红细胞上的C3b对I因子失活的敏感性低100倍。在22 ℃下，C3b、Bb在PNH红细胞上的半衰期是正常人红细胞上的三倍，并且与结合到不具有因子H样活性的颗粒上的酶的半衰期相似。这些观察结果表明，PNH红细胞对补体溶解的异常敏感性是由于正常人红细胞上存在的一种或多种因子H样蛋白的功能缺陷。
Erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) contained a subpopulation that lacked membrane-associated Factor H-like activity present on normal human erythrocytes. Initial deposition of C3b on the erythrocytes was effected using a fluid phase C3 convertase. The cells were then treated with fluorescein-labeled C3 and the cell-bound C3 convertase. Analysis utilizing the fluorescence- activated cell sorter revealed two distinct cell populations, one of which was highly fluorescent, indicating a large number of C3b molecules per cell. Only this population (43%) was susceptible to lysis (44%) when exposed to acidified serum before C3b deposition. The less fluorescent population resembled normal human erythrocytes and was not affected by prior treatment with acidified serum. Since C3b deposition occurred almost exclusively on the complement-sensitive cells in the PNH erythrocyte population, these cells could be examined for the Factor H-like regulatory activities without prior isolation. These functions include enhancement of inactivation of erythrocyte-bound C3b by Factor I and acceleration of the decay of erythrocyte-bound C3 convertase, C3b,Bb. It was found that C3b on PNH erythrocytes was 100- fold less susceptible to inactivation by Factor I than C3b on normal human erythrocytes. The half-life at 22 degrees C of C3b,Bb on PNH erythrocytes was threefold greater than on normal human erythrocytes and similar to that of the enzyme bound to particles that do not possess Factor H-like activity. These observations suggest that the abnormal susceptibility of PNH erythrocytes to lysis by complement is due to a functional deficiency in one or more of the Factor H-like proteins present on normal human erythrocytes.