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Identification and characterization of complement C3 receptors on human astrocytes
1Deptment of Medical Biochemistry, University of Wales College of Medicine, Cardiff, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|March 15, 1996
Summary
Astrocytes express complement receptors, including complement receptor 2 (CR2), which binds C3d and EBV gp340. This suggests a functional role for astrocyte CR2 in immune responses.
Area of Science:
- Neuroimmunology
- Complement System Biology
- Astrocyte Research
Background:
- Astrocytes are known to express complement components and are a significant source of intrathecal complement.
- The role of complement activation in astrocytes requires further investigation, particularly regarding complement receptor expression.
Purpose of the Study:
- To investigate the expression of complement receptors 1, 2, and 3 (CR1, CR2, CR3) in primary fetal astrocytes and astrocyte cell lines.
- To determine the functional significance of expressed complement receptors on astrocytes.
Main Methods:
- Analysis of CR1, CR2, and CR3 (CD35, CD21, CD11b/CD18) expression at protein and mRNA levels in primary astrocytes and cell lines.
- Reverse-transcriptase PCR and partial cDNA sequencing were used to confirm CR2 expression and analyze its structure.
- Functional assays involved assessing the binding of C3d and EBV gp340 to astrocyte CR2, with inhibition studies using anti-CR2 antibodies.
- Scatchard analysis was performed to quantify CR2 sites on astrocytes.
Main Results:
- CR3 was not expressed by any tested astrocyte cells.
- CR1 was expressed by primary astrocytes and one of four cell lines at both protein and mRNA levels.
- All primary astrocytes and cell lines expressed CR2 (CD21).
- Astrocyte CR2 cDNA showed homology to lymphocyte CR2 cDNA and exhibited an alternative splicing pattern of exon 11.
- Astrocyte CR2 demonstrated functional binding to C3d and EBV gp340, which was specifically blocked by anti-CR2 antibodies.
- Scatchard analysis revealed approximately 2000 functional CR2 sites per astrocyte with a Kd identical to that of B cells.
Conclusions:
- Astrocytes express functional complement receptor 2 (CR2/CD21), which binds complement fragment C3d and Epstein-Barr virus (EBV) surface protein gp340.
- The expression pattern and functional activity of astrocyte CR2 suggest a role in neuroinflammatory and immune processes within the central nervous system.
- Further research into astrocyte CR2 function could elucidate its involvement in neurological diseases.