title: Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice.
abstract: Hepatic Macs, consisting of resident KCs and infiltrating monocytes/IMs, are thought to play an important role in the pathogenesis of ALD. Previous work has focused on KCs or studied hepatic Macs as one cell population. The aim of the current study is to distinguish IMs from KCs and to compare their phenotypes and functions. We show here that a 4-week ethanol feeding of C57BL/6J mice causes recruitment of IMs into the liver. KCs and IMs can be distinguished based on their differential expression of F4/80 and CD11b. IMs can be divided further into two subsets based on their differential expression of Ly6C. KCs and two subsets of IMs were separately purified by FACS. The phagocytosis abilities and the expression profiles of genes related to various functions were compared among different populations of hepatic Macs. Ly6C(low) IMs exhibit an anti-inflammatory and tissue-protective phenotype; in contrast, Ly6C(hi) IMs exhibit a proinflammatory, tissue-damaging phenotype. The ratio of Ly6C(hi)/Ly6C(low) increases when mice chronically fed ethanol were binged, which significantly enhanced liver injury. Moreover, upon phagocytosis of apoptotic hepatocytes, Ly6C(hi) IMs switch to Ly6C(low) IMs. Taken together, chronic ethanol feeding induces the recruitment of two subsets of hepatic IMs, which play different or even opposite roles in regulating liver inflammation and repair. These findings may not only increase our understanding of the complex functions of Macs in the pathogenesis of ALD but also help us to identify novel therapeutic targets for the treatment of this disease.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences and.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, China;
authors.forename: Qiang
authors.initials: Q
authors.lastname: You
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences and.
authors.forename: Kenton
authors.initials: K
authors.lastname: Lor
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital, Jilin University, China; and.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences and Integrated Immunology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; cynthia.ju@ucdenver.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ju
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D005260:Female; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism; D010641:Phenotype
chemical_list: D000950:Antigens, Ly; D016898:Interferon-alpha; C494192:Ly-6C antigen, mouse; D007371:Interferon-gamma
keywords: Kupffer cells; M1 macrophages; M2 macrophages