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Defective complement receptors (CR1 and CR3) on erythrocytes and leukocytes of factor I (C3b-inactivator) deficient
Insights
Factor I deficiency in patients leads to low complement receptor 1 (CR1) on blood cells. This impacts CR1 function and phagocytosis, even when CR1 levels appear normal, suggesting C3b interaction causes receptor abnormalities.
Area of Science:
- Immunology
- Complement System Biology
Background:
- The complement system plays a crucial role in innate immunity.
- Complement receptor 1 (CR1) and CR3 are key receptors involved in immune cell function.
- Factor I deficiency leads to continuous presence of C3b in serum.
Purpose of the Study:
- To investigate the in vivo effects of constant C3b presence on CR1 and CR3 expression and function.
- To analyze CR1 and CR3 on peripheral blood cells of patients with genetic factor I deficiency.
Main Methods:
- Quantification of CR1 and CR3 using monoclonal antibodies.
- Functional assays including phagocytosis of opsonized erythrocytes and chemiluminescence.
- Analysis of peripheral blood cells from three factor I-deficient patients.
Main Results:
- Factor I-deficient patients showed significantly lower erythrocyte CR1 levels.
- Monocytes and neutrophils exhibited low CR1 numbers.
- Defective CR1-dependent phagocytosis and impaired chemiluminescence were observed in monocytes, even with normal CR1 levels.
- CR3-dependent monocyte function was also defective in most patients.
Conclusions:
- Constant C3b exposure in factor I deficiency leads to CR1 abnormalities on blood cells.
- These abnormalities impair CR1-mediated functions like phagocytosis and immune response.
- Factor I deficiency affects both CR1 and CR3 receptor functions.
Abstract:
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.