title: M1- and M2-macrophage polarization in thioacetamide (TAA)-induced rat liver lesions; a possible analysis for hepato-pathology.
abstract: "Classically activated macrophages (M1)" and "alternatively activated macrophages (M2)", which appear in injured tissues, control either inflammation or remodeling. The mechanism remains unclear. To clarify the M1-/M2-macrophage polarization in acute liver injury, M1- and M2-related factors were analysed in F344 rats by a single injection of TAA (300 mg/kg BW), and liver samples were collected on post injection (PI) hour 10 and days 1 to 10. Macrophage immunophenotypes were analyzed by single and double immunolabeling. M1-/M2-related factors were analyzed by real-time RT-PCR. On PI hour 10 (when centrilobular lesions were not still developed), expressions of IFN-γ, TNF-α, IL-1β, and IL-6 for M1, and IL-4 for M2 were already increased, followed by increased expressions of IL-10 and TGF-β1 for M2 on PI days 1-3 with development of centrilobular lesions and subsequent reparative fibrosis. On PI hour 10, CD204⁺ and MHC class II⁺ macrophages already increased in the intact periportal/Glisson's sheath regions, accompanied by an increased number of granzyme B⁺ NK cells. Reactive cells at PI hour 10 might produce M1-related factors. In addition to these macrophages, CD68⁺ and CD163⁺ macrophages, and CD3⁺ T cells appeared in the injured centrilobular region on PI days 1-3; there were macrophages reacting simultaneously to CD68/MHC class II, CD163/MHC class II, CD68/CD204, CD163/CD204, and MHC class II/CD204 in varying degrees. Although CD68⁺ and CD163⁺ macrophages are regarded as M1- and M2-types, respectively, the double labeling indicated that macrophage immunophenotypes are interchangeable in injured regions and subsequent fibrosis. An M1-/M2-macrophage paradigm would be useful to analyze hepatotoxicity and to understand the pathogenesis.
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Kavindra Kumara
authors.initials: KK
authors.lastname: Wijesundera
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Anusha Hemamali
authors.initials: AH
authors.lastname: Tennakoon
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Hossain M
authors.initials: HM
authors.lastname: Golbar
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Kato-Ichikawa
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Miyuu
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.affiliation: Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano city, Osaka. Japan. yamate@vet.osakafu-u.ac.jp.
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology* / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D016130:Immunophenotyping; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008297:Male; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide / Q000633:toxicity
chemical_list: D013853:Thioacetamide