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The membrane attack complex of complement induces caspase activation and apoptosis.
Alma J Nauta1, Mohamed R Daha, Odette Tijsma
1Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. nauta@LUMC.nl
European Journal of Immunology
|March 1, 2002
Summary
The terminal complement pathway, specifically the C5b-9 complex, triggers programmed cell death (apoptosis) in cells. This complement-mediated apoptosis is caspase-dependent and occurs even without cell lysis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The terminal complement pathway forms C5b-9 complexes, potentially causing cell lysis.
- Emerging evidence suggests the terminal complement pathway can induce apoptosis in vivo.
Purpose of the Study:
- To investigate the role of complement in inducing apoptosis in vitro.
- To elucidate the specific mechanisms and components involved in complement-induced cell death.
Main Methods:
- Rat mesangial cells were treated with complement-activating antibodies and serum.
- Apoptosis was assessed by phosphatidylserine exposure and nuclear fragmentation.
- Caspase activity was measured, and the effect of a pan-caspase inhibitor (zVAD-fmk) was evaluated.
- Cells were also exposed to purified C5b-9 complexes.
Main Results:
- Complement activation induced time- and dose-dependent apoptosis in rat mesangial cells.
- Apoptosis was inhibited by C6-deficient serum and completely blocked by zVAD-fmk.
- Complement induced caspase 3 activation.
- Purified C5b-9 complexes alone induced caspase activation and apoptosis.
Conclusions:
- C5b-9 complexes are key mediators of complement-induced apoptosis.
- This apoptosis occurs via a caspase-dependent pathway.
- Complement-mediated apoptosis may contribute to inflammatory conditions like hyperacute xenograft rejection.