Increased sensitivity of early apoptotic cells to complement-mediated lysis
Gitit Attali1, Dana Gancz, Zvi Fishelson
1Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
European Journal of Immunology
|September 16, 2004
Summary
Early apoptotic cells become vulnerable to complement-mediated lysis, a process dependent on caspase activation. Enhanced Bcl-2 expression can protect cells from this necrotic-type death.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- The complement system aids in clearing apoptotic cells via phagocytosis.
- The direct lytic effects of complement on apoptotic cells remain poorly understood.
- Apoptosis involves programmed cell death, but its interaction with complement lysis is unclear.
Purpose of the Study:
- To investigate the sensitivity of early apoptotic cells to complement-mediated lysis.
- To determine the role of caspases and Bcl-2 in complement lysis of apoptotic cells.
- To explore whether apoptotic cells are susceptible to other pore-forming agents.
Main Methods:
- Jurkat and Raji cells were induced into early apoptosis using anti-Fas antibody, staurosporine, or etoposide.
- Complement-mediated lysis was assessed, along with the deposition of complement proteins C3 and C9.
- The effects of pan-caspase and specific caspase inhibitors, as well as Bcl-2 expression, were analyzed.
Main Results:
- Early apoptotic cells exhibited increased sensitivity to lysis by antibody and complement compared to control cells.
- Enhanced deposition of C3 and C9 was observed on apoptotic cells, blocked by caspase inhibitors.
- Apoptotic cells were also more sensitive to pore formers (streptolysin O, melittin), and Bcl-2 overexpression reduced complement sensitivity.
Conclusions:
- Early apoptotic cells, post-caspase activation, become susceptible to complement-mediated necrotic-type lysis.
- Caspase activity is crucial for the enhanced sensitivity of apoptotic cells to complement lysis.
- Bcl-2 plays a protective role against complement-mediated lysis in Jurkat cells.
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