Cooperation between decay-accelerating factor and membrane cofactor protein in protecting cells from autologous
W G Brodbeck1, C Mold, J P Atkinson
1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 18, 2000
Summary
Decay-accelerating factor (DAF) and membrane cofactor protein (MCP) work together to prevent complement system damage to self cells. DAF is essential for MCP to effectively cleave complement proteins, enhancing cellular protection.
Area of Science:
- Immunology
- Complement System Biology
Background:
- Decay-accelerating factor (DAF or CD55) and membrane cofactor protein (MCP or CD46) protect self cells from complement activation.
- The cooperative mechanisms of DAF and MCP in regulating autologous complement remain unclear.
Purpose of the Study:
- To investigate the synergistic functions of DAF and MCP in regulating complement intermediates.
- To elucidate the cooperative mechanisms between DAF and MCP on cell surfaces.
Main Methods:
- Generated a GPI-anchored form of MCP for cell membrane incorporation.
- Utilized purified alternative pathway complement components and rabbit erythrocytes for quantitative assays.
- Examined complement intermediates with individual or combined DAF and MCP.
Main Results:
- DAF and MCP synergistically inhibit C3b deposition on cell surfaces.
- MCP's factor I-mediated C3b cleavage activity is inhibited by factors B and D.
- DAF restores MCP's C3b cleavage activity in the presence of factors B and D.
Conclusions:
- The combined action of DAF and MCP exceeds their individual contributions to complement regulation.
- DAF is crucial for MCP's function in cleaving cell-bound C3b, particularly when factors B and D are present.
- Findings have implications for xenotransplantation, inflammatory diseases, and tumor immune evasion.
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