title: Activation and increase of radio-sensitive CD11b+ recruited Kupffer cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice.
abstract: We have recently reported that Kupffer cells consist of two subsets, radio-resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+ Kupffer cells/macrophages (Mφs). Non-alcoholic steatohepatitis (NASH) is characterized not only by hepatic steatosis but also chronic inflammation and fibrosis. In the present study, we investigated the immunological mechanism of diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice. After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed severe steatohepatitis and fibrosis resembling human NASH. F4/80+ Mφs which were both CD11b and CD68 positive accumulated in the liver. The production of TNF and FasL indicated that they are the pivotal effectors in this hepatitis. The weak phagocytic activity and lack of CRIg mRNA suggested that they were recruited Mφs. Intermittent exposure to 1 Gy irradiation markedly decreased these Mφs and dramatically inhibited liver inflammation without attenuating steatosis. However, depletion of the resident subset by clodronate liposome (c-lipo) treatment increased the Mφs and tended to exacerbate disease progression. Recruited CD11b+ CD68+ Kupffer cells/Mφs may play an essential role in steatohepatitis and fibrosis in FGF5 null mice fed with a HFD. Recruitment and activation of bone marrow derived Mφs is the key factor to develop steatohepatitis from simple steatosis.
authors.affiliation: Department of Immunology and Microbiology National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakashima
authors.affiliation: Department of Immunology and Microbiology National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Immunology and Microbiology National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department of Immunology and Microbiology National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Ikarashi
authors.affiliation: Department of Traumatology National Defense Medical College Research Institute, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Developmental Anatomy and Regenerative Biology National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hanaka
authors.affiliation: Department of Developmental Anatomy and Regenerative Biology National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Imaki
authors.affiliation: Department of Immunology and Microbiology National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
mesh_terms: D000818:Animals; D039481:CD11b Antigen; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051521:Fibroblast Growth Factor 5 / Q000172:deficiency*; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D039481:CD11b Antigen; D004041:Dietary Fats; C496450:Fgf5 protein, mouse; D051521:Fibroblast Growth Factor 5