       Document 0468
 DOCN  M9460468
 TI    Proteolytic cleavage of CR1 on human erythrocytes in vivo: evidence for
       enhanced cleavage in AIDS.
 DT    9404
 AU    Pascual M; Danielsson C; Steiger G; Schifferli JA; Laboratoire
       d'Immunonephrologie, Centre Medical Universitaire,; Geneva, Switzerland.
 SO    Eur J Immunol. 1994 Mar;24(3):702-8. Unique Identifier : AIDSLINE
       MED/94170847
 AB    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.
 DE    Acquired Immunodeficiency Syndrome/*BLOOD  Antigens,
       CD/CHEMISTRY/METABOLISM  Cell Separation  Erythrocyte Aging  Erythrocyte
       Membrane/*METABOLISM  Human  Membrane Glycoproteins/CHEMISTRY/METABOLISM
       Papain/PHARMACOLOGY  Peptide Mapping  Receptors, Complement
       3b/CHEMISTRY/*METABOLISM  Support, Non-U.S. Gov't  Trypsin/PHARMACOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

