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Fu X , Ju J , Lin Z , Xiao W , Li X , Zhuang B , Zhang T , Ma X , Li X , Ma C , Su W , Wang Y , Qin X , Liang S
Target deletion of complement component 9 attenuates antibody-mediated hemolysis and lipopolysaccharide (LPS)-induced acute shock in mice
Sci Rep. 2016 Jul 22;6 :30239
PMID: 27444648    PMCID: PMC4957234   
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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-1beta 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.
Notes
2045-2322 Fu, Xiaoyan Ju, Jiyu Lin, Zhijuan Xiao, Weiling Li, Xiaofang Zhuang, Baoxiang Zhang, Tingting Ma, Xiaojun Li, Xiangyu Ma, Chao Su, Weiliang Wang, Yuqi Qin, Xuebin Liang, Shujuan R01 HL130233/HL/NHLBI NIH HHS/United States R01 CA166144/CA/NCI NIH HHS/United States P30 MH092177/MH/NIMH NIH HHS/United States R01 AI061174/AI/NIAID NIH HHS/United States P30 CA006927/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England Sci Rep. 2016 Jul 22;6:30239. doi: 10.1038/srep30239.