Pascual M, Danielsson C, Steiger G, Schifferli J A
Laboratoire d'Immunonéphrologie, Centre Médical Universitaire, Geneva, Switzerland.
Eur J Immunol. 1994 Mar;24(3):702-8. doi: 10.1002/eji.1830240332.
The number of complement receptor type 1 (CR1; CD35) on human erythrocytes (E) decreases during normal in vivo aging. Patients with acquired immunodeficiency syndrome (AIDS) have an acquired deficiency of CR1 on E. The possible mechanisms responsible for the loss of CR1 from E include the release of small vesicles from the E membrane and proteolytic cleavage of CR1. When compared to E of normal donors and of asymptomatic human immunodeficiency virus HIV+ subjects, E of patients with AIDS had fewer CR1/E (p < 0.001), but had the same number of two glycosylphosphatidylinositol-anchored proteins, decay-accelerating-factor (DAF) and CD59. When compared to young E, old E separated by density gradients on Percoll had fewer CR1 [six normal subjects, mean loss: 50.4 +/- 4.9 (SEM) %], DAF (34.4 +/- 1.2%) and CD59 (34.5 +/- 2.7%). The loss of CR1 was significantly higher than the loss of DAF and CD59 (p < 0.02). In vitro, ATP depletion of E is responsible for the release of vesicles from the E surface, a reaction that has been called in vitro aging. CR1, DAF and CD59 were lost on ATP-depleted E; however, the loss of CR1 and DAF were identical (six experiments, mean loss of CR1: 28.7 +/- 2.7%, DAF: 26.3 +/- 4.6% and CD59: 20.5 +/- 4%). Thus, the release of vesicles from E cannot explain the specific loss of CR1 in patients with AIDS and would explain only incompletely the loss of CR1 during in vivo aging. In vitro experiments indicated that CR1 was more sensitive to trypsin and papain cleavage than DAF and CD59. Enhanced chemiluminescence Western blotting, using a monoclonal antibody (E11) recognizing fragments of CR1 down to 43 kDa on E exposed to trypsin or papain, indicated that normal E bear fragments of CR1, which are not found on polymorphonuclear leukocytes or on CR1-bearing vesicles in urine. The relative amount of these fragments was increased in patients with AIDS. Taken together these data suggest that the specific loss of CR1 on E in AIDS is due to proteolytic cleavage. The loss of CR1 during in vivo aging also involves proteolytic cleavage, although part of the loss might be explained by other mechanisms including the release of vesicles by E.
在正常体内衰老过程中，人类红细胞（E）上的1型补体受体（CR1；CD35）数量会减少。获得性免疫缺陷综合征（AIDS）患者的红细胞上存在CR1获得性缺陷。红细胞上CR1丢失的可能机制包括红细胞膜释放小泡以及CR1的蛋白水解切割。与正常供体和无症状人类免疫缺陷病毒（HIV）阳性受试者的红细胞相比，AIDS患者的红细胞上CR1/E较少（p < 0.001），但两种糖基磷脂酰肌醇锚定蛋白，即衰变加速因子（DAF）和CD59的数量相同。与年轻红细胞相比，通过Percoll密度梯度分离的老年红细胞CR1较少[6名正常受试者，平均丢失：50.4 +/- 4.9（SEM）%]，DAF较少（34.4 +/- 1.2%），CD59较少（34.5 +/- 2.7%）。CR1的丢失显著高于DAF和CD59的丢失（p < 0.02）。在体外，红细胞的ATP耗竭会导致红细胞表面释放小泡，这一反应被称为体外衰老。ATP耗竭的红细胞上CR1、DAF和CD59都会丢失；然而，CR1和DAF的丢失是相同的（6次实验，CR1平均丢失：28.7 +/- 2.7%，DAF：26.3 +/- 4.6%，CD59：20.5 +/- 4%）。因此，红细胞释放小泡无法解释AIDS患者中CR1的特异性丢失，也只能部分解释体内衰老过程中CR1的丢失。体外实验表明，CR1比DAF和CD59对胰蛋白酶和木瓜蛋白酶的切割更敏感。使用识别经胰蛋白酶或木瓜蛋白酶处理的红细胞上低至43 kDa的CR1片段的单克隆抗体（E11）进行增强化学发光免疫印迹分析表明，正常红细胞带有CR1片段，而多形核白细胞或尿液中携带CR1的小泡上未发现这些片段。AIDS患者中这些片段的相对量增加。综合这些数据表明，AIDS患者红细胞上CR1的特异性丢失是由于蛋白水解切割。体内衰老过程中CR1的丢失也涉及蛋白水解切割，尽管部分丢失可能由包括红细胞释放小泡在内的其他机制解释。
