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Mechanisms of complement resistance induced by non-lethal complement attack and by growth arrest
K J Marchbank1, C W van den Berg, B P Morgan
1Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, UK.
Immunology
|April 1, 1997
Summary
Non-lethal complement attack on K562 cells induces resistance, but not via known inhibitors like CD59. This resistance may stem from novel factors or metabolic changes, indicating cells actively manage complement-mediated killing.
Area of Science:
- Immunology
- Cell Biology
Background:
- Non-lethal complement (C) exposure can transiently protect cells from lethal C attack.
- Phorbol 12-myristate 13-acetate (PMA) treatment increases CD59 expression and C resistance in K562 cells.
Purpose of the Study:
- To investigate if non-lethal C attack induces C resistance in K562 cells similarly to PMA treatment.
- To explore the mechanisms underlying C resistance in K562 cells under different conditions.
Main Methods:
- Assessing expression of C inhibitors (DAF, MCP, CD59) on K562 cells after non-lethal C attack.
- Neutralizing known C inhibitors with blocking antibodies.
- Inducing C resistance in growth-arrested K562 cells and examining inhibitor levels.
- Comparing the kinetics of C resistance in non-lethally attacked vs. growth-arrested cells.
Main Results:
- Non-lethal C attack did not alter DAF, MCP, or CD59 expression on K562 cells, and antibody neutralization did not reverse resistance.
- Growth-arrested K562 cells showed C resistance with unaltered DAF/MCP but reduced CD59.
- Non-lethal C attack further increased resistance in growth-arrested cells, suggesting distinct mechanisms.
- Resistance after non-lethal attack lasted <8 hours, while resistance in growth-arrested cells persisted up to 48 hours.
Conclusions:
- C resistance induced by non-lethal attack or growth arrest in K562 cells is not mediated by known membrane C inhibitors (DAF, MCP, CD59).
- Mechanisms may involve novel inhibitors or metabolic depletion, common to both conditions.
- Cells appear to play an active role in modulating their susceptibility to C-mediated killing.