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Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism
T J Oglesby1, C J Allen, M K Liszewski
1Division of Rheumatology, Howard Hughes Medical Institute, St. Louis, Missouri.
The Journal of Experimental Medicine
|June 1, 1992
Summary
Membrane cofactor protein (MCP) protects host cells from complement system damage. This study shows MCP reduces complement C3b deposition and prevents cell lysis, highlighting its intrinsic cytoprotective mechanism.
Area of Science:
- Immunology
- Cell Biology
Background:
- Complement (C) activation is crucial in immune responses, involving C3 cleavage.
- Regulators of C activation proteins, like Membrane Cofactor Protein (MCP), control this process.
- MCP acts as a cofactor for factor I, inactivating C3b and C4b, thus protecting host cells.
Purpose of the Study:
- To investigate the relationship between MCP expression, C3b deposition, and cellular protection.
- To determine if MCP confers protection against complement-mediated lysis in transfected cells.
Main Methods:
- NIH/3T3 cells were transfected with human MCP.
- Transfected cells were exposed to human serum (complement source) and anti-mouse antibody.
- C3b deposition and cell lysis were quantified to assess MCP's effect.
Main Results:
- MCP expression inhibited C3b deposition in a dose-dependent manner.
- MCP significantly reduced the lysis of cells expressing it.
- MCP did not protect bystander cells, indicating a cell-intrinsic protective mechanism.
Conclusions:
- MCP plays a critical role in protecting host cells from complement-mediated damage.
- MCP functions at the cellular level through an intrinsic mechanism to prevent complement activation.
- These findings underscore MCP's importance in preventing inadvertent complement activation on host tissues.