Defective complement receptors (CR1 and CR3) on erythrocytes and leukocytes of factor I (C3b-inactivator) deficient patients.
In view of a possible modulation of the C3b receptor (CR1) by its ligand, we studied a situation in vivo in which C3b is constantly present in the serum, i.e. the genetic factor I-deficiency. C3b and iC3b receptors (CR1, CR3) on peripheral blood cells, were analysed in three I-deficient (I-def.) patients, from two unrelated families. CR1 and CR3 were quantified by means of monoclonal antibodies, and functionally tested (phagocytosis of sensitized sheep erythrocytes (EIgG) or rabbit erythrocytes (Er), coated with C3b, and chemiluminescence (CL) induced by serum-opsonized zymosan). Erythrocyte CR1 levels were significantly lower in I-def. patients than in normal individuals. Monocytes and polymorphonuclear neutrophils (PMN) prepared at 4 degrees C, to prevent increase of CR1 expression in vitro, expressed low CR1 numbers. Monocytes prepared at room temperature showed a defective CR1-dependent phagocytosis and an impaired CL response, although their CR1 levels were found normal in these conditions. This discrepancy was also observed on phorbol myristate acetate (PMA)-activated cells. These CR1 abnormalities are likely to result from repeated interactions of CR1 with C3b molecules, which circulated in the serum of I-def. patients and were deposited onto their red cells. Although iC3b, the CR3 ligand, is not produced in I-deficient sera, monocyte CR3-dependent function (phagocytosis of unopsonized Er) was also found to be defective in two out of the three patients.
D002648:Child; D003180:Complement C3b Inactivator Proteins / Q000172:deficiency*; D004912:Erythrocytes / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D016177:Macrophage-1 Antigen; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D011951:Receptors, Complement / Q000032:analysis / Q000276:immunology*; D017463:Receptors, Complement 3b; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan
D003180:Complement C3b Inactivator Proteins; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate