title: Anti-CD24 neutralizing antibody exacerbates Concanavalin A-induced acute liver injury in mice via liver M1 macrophages.
abstract: Liver largely relies on its innate immunity to initiate quick and effective defense against potentially toxic agents, and innate immune cells are major players in this process. However, excessive inflammation due to out-of-control immune response may eventually cause liver injury. Thus, it is important to fully understand the regulatory mechanisms associated with liver inflammation. Here we showed that anti-CD24 neutralizing antibody exacerbated hepatic inflammation in a Con A-induced acute liver injury murine model. Our results supported that hepatic macrophages were required for anti-CD24 neutralizing antibody-aggravated liver inflammation, as depletion of macrophages significantly alleviated Con A-induced inflammation. M1 macrophages, but not M2 macrophages, were specifically induced by Con A, and more greatly by Con A in combination with anti-CD24 neutralizing antibody. The combined treatment further promoted M1 hepatic macrophages to express TNF-α, which increased hepatocytes apoptosis. Taken together, these data suggest that anti-CD24 neutralizing antibody plays an important role in aggravating inflammation in the process of Con A-induced acute liver injury in mice. The possible mechanism might involve the enhanced secretion of TNF-α by hepatic M1 macrophages. This study also implicates a role for CD24 in negative regulation of Con A-induced liver inflammation.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China; Department of Laboratory Medicine, Xiqing Hospital of Tianjin, Tianjin 300380, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hai
authors.affiliation: Department of Breast and Thyroid Surgery, Shaoxing People's Hospital and Shaoxing Hospital of Zhejiang University, Shaoxing 312000, China.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yatong
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Clinical Laboratory, College of Stomatology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Medical English and Health Communication, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, Tianjin Medical University, Tianjin 300070, China. Electronic address: xjzh@tmu.edu.cn.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D057134:Antibodies, Neutralizing / Q000009:adverse effects*; D051927:CD24 Antigen / Q000037:antagonists & inhibitors*; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D003208:Concanavalin A / Q000009:adverse effects*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007728:Kupffer Cells / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D051927:CD24 Antigen; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A
keywords: Acute liver injury; CD24; Concanavalin A (Con A); Liver M1 macrophage; TNF-α