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Updated: Mar 17, 2026
Depletion of Specific Cell Populations by Complement Depletion
Published on: February 5, 2010
Target deletion of complement component 9 attenuates antibody-mediated hemolysis and lipopolysaccharide (LPS)-induced
Xiaoyan Fu1, Jiyu Ju1, Zhijuan Lin1
1Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
Insights
Scientists generated C9-deficient mice to study the membrane attack complex (MAC). These mice showed reduced hemolysis and LPS-induced shock, highlighting MAC
Area of Science:
- Immunology
- Complement system
- Molecular biology
Background:
- The terminal complement cascade forms the membrane attack complex (MAC), C5b-9, which can lyse cells.
- Previous studies on MAC function used C5 or C6 deficient mice or CD59 regulators.
- A C9-deficient mouse model was lacking to specifically investigate the role of C5b-9.
Purpose of the Study:
- To generate and characterize a mouse model deficient in C9 (mC9(-/-)).
- To dissect the specific role of C5b-9 in complement-mediated hemolysis and disease pathogenesis.
- To investigate the involvement of C5b-9 in inflammasome activation.
Main Methods:
- Generation of C9-deficient mice (mC9(-/-)).
- Assessment of anti-erythrocyte antibody-mediated hemolysis in mC9(-/-) mice.
- Evaluation of lipopolysaccharide (LPS)-induced acute shock and IL-1β release in mC9(-/-) mice.
Main Results:
- The generated mC9(-/-) mice successfully lacked C9.
- Absence of C9 significantly attenuated anti-erythrocyte antibody-mediated hemolysis.
- mC9(-/-) mice exhibited reduced severity of LPS-induced acute shock, correlating with decreased IL-1β release and suppressed MAC-mediated inflammasome activation.
Conclusions:
- The study successfully generated mC9(-/-) mice, providing a valuable tool to study MAC function.
- Results confirm the critical role of C5b-9 in complement-mediated hemolysis.
- The findings highlight the significant involvement of C5b-9 in inflammasome activation and associated pathologies.
Abstract:
Terminal complement membrane attack complex (MAC) formation is induced initially by C5b, followed by the sequential condensation of the C6, C7, C8. Polymerization of C9 to the C5b-8 complex forms the C5b-9 (or MAC). The C5b-9 forms lytic or non lytic pores in the cell membrane destroys membrane integrity. The biological functionalities of MAC has been previously investigated by using either the mice deficient in C5 and C6, or MAC's regulator CD59. However, there is no available C9 deficient mice (mC9(-/-)) for directly dissecting the role of C5b-9 in the pathogenesis of human diseases. Further, since C5b-7 and C5b-8 complexes form non lytic pore, it may also plays biological functionality. To better understand the role of terminal complement cascades, here we report a successful generation of mC9(-/-). We demonstrated that lack of C9 attenuates anti-erythrocyte antibody-mediated hemolysis or LPS-induced acute shock. Further, the rescuing effect on the acute shock correlates with the less release of IL-1β in mC9(-/-), which is associated with suppression of MAC-mediated inflammasome activation in mC9(-/-). Taken together, these results not only confirm the critical role of C5b-9 in complement-mediated hemolysis and but also highlight the critical role of C5b-9 in inflammasome activation.
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