PROTEOLYTIC CLEAVAGE OF CR-1 ON HUMAN ERYTHROCYTES IN-VIVO - EVIDENCEFOR ENHANCED CLEAVAGE IN AIDS

The number of complement receptor type 1 (CR1; CD35) on human erythroc ytes (E) decreases during normal in vivo aging. Patients with acquired immunodefiziency syndrome (AIDS) have an acquired deficiency of CR1 o n E. The possible mechanisms responsible for the loss of CR1 from E in clude the release of small vesicles from the E membrane and proteolyti c cleavage of CR1. When compared to E of normal donors and of asymptom atic human immunodeficiency virus HIV+ subjects, E of patients with AI DS had fewer CR1/E (p < 0.001), but had the same number of two glycosy lphosphatidyl-inositol-anchored proteins, decay-accelerating-factor (D AF) and CD59. When compared to young E, old E separated by density gra dients 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 l oss 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 lo ss of CR1 and DAF were identical (six experiments, mean loss for 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 mor e sensitive to trypsin and papain cleavage than DAF and CD59. Enhanced chemiluminescence Western blotting, using a monoclonal antibody (Ell) recognizing fragments of CR1 down to 43 kDa on E exposed to trypsin o r papain, indicated that normal E bear fragments of CR1, which are not found on polymorphonuclear leukocytes or on CR1-bearing vesicles in u rine. The relative amount of these fragments was increased in patients with AIDS. Taken together these data suggest that the specific loss o f CR1 on E in AIDS is due to proteolytic cleavage. The loss of CR1 dur ing 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.