ACTIVATION OF THE ALTERNATIVE COMPLEMENT PATHWAY BY EXPOSURE OF PHOSPHATIDYLETHANOLAMINE AND PHOSPHATIDYLSERINE ON ERYTHROCYTES FROM SICKLE-CELL DISEASE PATIENTS
ACTIVATION OF THE ALTERNATIVE COMPLEMENT PATHWAY BY EXPOSURE OF PHOSPHATIDYLETHANOLAMINE AND PHOSPHATIDYLSERINE ON ERYTHROCYTES FROM SICKLE-CELL DISEASE PATIENTS
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DOI：
10.1172/jci116706
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发表时间：
1993-09-01
影响因子：
15.9
通讯作者：
MOLD, C
中科院分区：
文献类型：
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作者：
WANG, RH;PHILLIPS, G;MOLD, C
镰状细胞性贫血（SCA）患者红细胞的脱氧改变膜磷脂分布，增加暴露于外小叶的磷脂酰乙醇胺（PE）和磷脂酰丝氨酸（PS）。本研究探讨镰状红细胞膜磷脂暴露改变是否导致补体活化。用C3结合法测定镰状红细胞体外脱氧而非正常红细胞的补体活化。其他证据表明，这种激活是膜磷脂改变的结果。首先，补体在与四硫酸钠孵育后被正常红细胞激活，产生类似的磷脂变化。其次，镰状细胞或四硫酸处理的红细胞活化补体不需要抗体。第三，镰状红细胞和四硫代酸处理红细胞的膜调节蛋白，衰变加速因子（CD55）和C3b/C4b受体（CD35）正常。最后，将PE或PS注入正常红细胞可诱导其他途径激活。危重期SCA患者血浆因子Bb水平高于基线水平，从住院SCA患者分离的红细胞中结合C3水平升高，表明体内发生了替代途径激活。激活补体可能是镰状危象发作的一个促成因素，缩短红细胞的寿命，降低宿主对感染的防御能力。
Deoxygenation of erythrocytes from sickle cell anemia (SCA) patients alters membrane phospholipid distribution with increased exposure of phosphatidylethanolamine (PE) and phosphatidylserine (PS) on the outer leaflet. This study investigated whether altered membrane phospholipid exposure on sickle erythrocytes results in complement activation. In vitro deoxygenation of sickle but not normal erythrocytes resulted in complement activation measured by C3 binding. Additional evidence indicated that this activation was the result of the alterations in membrane phospholipids. First, complement was activated by normal erythrocytes after incubation with sodium tetrathionate, which produces similar phospholipid changes. Second, antibody was not required for complement activation by sickle or tetrathionate-treated erythrocytes. Third, the membrane regulatory proteins, decay-accelerating factor (CD55) and the C3b/C4b receptor (CD35), were normal on sickle and tetrathionate-treated erythrocytes. Finally, insertion of PE or PS into normal erythrocytes induced alternative pathway activation. SCA patients in crisis exhibited increased plasma factor Bb levels compared with baseline, and erythrocytes isolated from hospitalized SCA patients had increased levels of bound C3, indicating that alternative pathway activation occurs in vivo. Activation of complement may be a contributing factor in sickle crisis episodes, shortening the life span of erythrocytes, and decreasing host defense against infections.