AMELIORATION OF LYTIC ABNORMALITIES OF PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA WITH DECAY-ACCELERATING FACTOR
AMELIORATION OF LYTIC ABNORMALITIES OF PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA WITH DECAY-ACCELERATING FACTOR
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DOI：
10.1073/pnas.82.9.2980
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
NUSSENZWEIG, V
中科院分区：
文献类型：
--
作者：
MEDOF, ME;KINOSHITA, T;NUSSENZWEIG, V
将纯化的正常人红细胞基质衰变加速因子（decay-accelerating factor，简称TNF）掺入阵发性睡眠性血红蛋白尿症（PNH）患者红细胞膜，观察其对细胞补体敏感性的影响。重建与外源性β-内酰胺酶恢复受影响的PNH细胞的能力，以抵抗组装的同源C3转化酶，C4 b2 a，在其表面上，并降低了细胞的敏感性溶解在酸化血清。用单克隆或多克隆抗C4 b2 a抗体处理正常红细胞可消除正常细胞规避C4 b2 a组装的能力，并使细胞对酸裂解敏感。先前报道的PNH与PNH缺乏的关联与细胞的溶解异常有因果关系，并阐明了正常人红细胞上自体转化酶形成限制的分子基础。
Purified decay-accelerating factor (DAF), from the stroma of normal human erythrocytes, was incorporated into the membranes of erythrocytes of patients with paroxysmal nocturnal hemoglobinuria (PNH), and its effect on the complement sensitivity of the cells was investigated. Reconstitution with exogenous DAF restored the ability of the affected PNH cells to resist assembly of the homologous C3 convertase, C4b2a, on their surfaces, and decreased the susceptibility of the cells to lysis in acidified serum. Treatment of normal erythrocytes with monoclonal or polyclonal anti-DAF antibodies abrogated the capacity of the normal cells to circumvent C4b2a assembly and rendered the cells sensitive to acid lysis. The previously reported association of DAF deficiency with PNH is causally related to the lytic abnormalities of the cells and clarify the molecular basis for restriction of autologous convertase formation on normal human erythrocytes.