DEFICIENCY OF AN ERYTHROCYTE-MEMBRANE PROTEIN WITH COMPLEMENT REGULATORY ACTIVITY IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA
DEFICIENCY OF AN ERYTHROCYTE-MEMBRANE PROTEIN WITH COMPLEMENT REGULATORY ACTIVITY IN PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA
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DOI：
10.1073/pnas.80.17.5430
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
MULLEREBERHARD, HJ
中科院分区：
文献类型：
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作者：
PANGBURN, MK;SCHREIBER, RD;MULLEREBERHARD, HJ
阵发性睡眠性血红蛋白尿(PNH)是一种获得性溶血性贫血，其红细胞对补体的溶解异常敏感。PNH红细胞膜相关补体调节剂的功能缺陷已被证实。从正常人红细胞中分离出2因子类H蛋白C3b受体(CR1)和衰变加速因子(DAF)，并制备了特异性抗血清。抗血清对正常红细胞的选择性抑制表明，导致红细胞结合C3转换酶加速衰退的因子是DAF，而使红细胞结合C3b失活的辅因子是CR1。PNH红细胞缺乏这两种活性。CR1缺陷的红细胞显示出正常的DAF活性，但没有凝血因子I辅因子活性。这些细胞在酸化的人血清中对补体介导的裂解不敏感，而PNH红细胞和经链霉蛋白酶处理的人红细胞(缺乏DAF和CR1活性)可通过这种处理裂解。显然，主要负责阻止正常人红细胞补体激活的蛋白质是DAF。用抗DAF抗体从1例PNH患者的正常红细胞膜中分离到一种相对分子质量为73,000的蛋白，提示PNH细胞缺乏DAF蛋白。而异常的PNH红细胞上存在CR1抗原。显然，PNH临床表现的主要分子缺陷可能是膜相关DAF蛋白的缺乏，异常细胞也可能表现出CR1功能受损。
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which the erythrocytes are abnormally sensitive to lysis by complement. A functional deficiency of membrane-associated complement regulators has been demonstrated on PNH erythrocytes. The 2 factor H-like proteins, the C3b receptor (CR1) and the decay-accelerating factor (DAF), were isolated from normal human erythrocytes, and specific antisera were prepared. Selective inhibition of the 2 proteins on normal erythrocytes by the antisera demonstrated that the factor responsible for accelerated decay of erythrocyte-bound C3 convertase is DAF and that the cofactor required for inactivation of erythrocyte-bound C3b by factor I is CR1. PNH erythrocytes wree deficient in both of these activities. Erythrocytes deficient in CR1, which were obtained from an apparently healthy individual, exhibited normal DAF activity but no factor I cofactor activity. These cells were not susceptible to complement-mediated lysis in acidified human serum, whereas PNH erythrocytes and pronase-treated human erythrocytes (which lack DAF and CR1 activities) were lysed by this treatment. Evidently, the protein primarily responsible for preventing complement activation on normal human erythrocytes is DAF. A MW 73,000 protein isolated from the normal erythrocyte membranes of 1 PNH patient by using anti-DAF IgG was largely absent from the abnormal erythrocytes of this individual, suggesting that PNH cells lack the DAF protein. CR1 antigen, however, was present on the abnormal PNH erythrocytes. Evidently, the primary molecular defect underlying the clinical manifestations of PNH may be the lack of the membrane-associated DAF protein and that the abnormal cells may also exhibit impaired CR1 function.