title: Target deletion of complement component 9 attenuates antibody-mediated hemolysis and lipopolysaccharide (LPS)-induced acute shock in mice.
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.
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Fu
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Ju
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Zhijuan
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Baoxiang
authors.initials: B
authors.lastname: Zhuang
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Ma
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Su
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA19140, USA.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Qin
authors.affiliation: Key Lab for Immunology in Universities of Shandong Province, School of Clinical Medicine, Weifang Medical University, Weifang, 261053, P.R.China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Liang
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D050776:Complement C5b / Q000235:genetics* / Q000276:immunology; D003186:Complement C9 / Q000235:genetics* / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D012769:Shock / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology
chemical_list: D000906:Antibodies; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D058847:Inflammasomes; D008070:Lipopolysaccharides; D050776:Complement C5b; D003165:Complement System Proteins