title: Slowly progressive cholangiofibrosis induced in rats by α-naphthylisothiocyanate (ANIT), with particular references to characteristics of macrophages and myofibroblasts.
abstract: A progressive cholangiofibrosis was developed as an animal model in 6-week-old male F344 rats by repeated intraperitoneal injections of α-naphthylisothiocyanate (ANIT) for 19 weeks; liver samples were examined at post-first injection (PFI) weeks 3, 7, 10, 13, 16 and 19, focusing on characteristics of macrophages and myofibroblasts by immunohistochemical analyses. In the affected Glisson's sheath consisting of inflammatory cell infiltrates, bile duct proliferation and advancing fibrosis, the number of macrophages reacting to OX6 (recognizing MHC class II) increased consistently (PFI weeks 3-19), suggesting a central role of antigen presenting cells in the biliary fibrosis; macrophages reacting to ED1 (CD68, reflecting phagocytic activity) and ED2 (CD163, relating to proinflammatory factor production) showed a significantly increased number at PFI weeks 7-19 and PFI weeks 13-19, respectively. Interestingly, macrophages positive for SRA-E5 (CD204, reflecting lipid metabolism) increased at PFI weeks 7-19, and the appearance was limited in the sinusoids around the affected Glisson's sheath. Myofibroblasts appearing in the affected Glisson's sheath reacted to vimentin and desmin at early (PFI weeks 3-7) and mid (PFI weeks 10-13) stages, and then they came to strongly express α-smooth muscle actin at late stage (PFI weeks 16-19). This study shows that macrophages exhibit heterogeneous properties depending on stages and locations; in association with such macrophage populations, myofibroblasts expressing various cytoskeletons participate in cholangiofibrosis. These characteristics would be useful in evaluating the pathogenesis of possible cholangio-toxicants.
authors.affiliation: Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-ourai-kita, Izumisano City, Osaka 598-8531, Japan.
authors.forename: Hossain M
authors.initials: HM
authors.lastname: Golbar
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.forename: Chisa
authors.initials: C
authors.lastname: Ichikawa
authors.forename: Miyuu
authors.initials: M
authors.lastname: Tanaka
authors.forename: Vetnizah
authors.initials: V
authors.lastname: Juniantito
authors.forename: Osamu
authors.initials: O
authors.lastname: Sawamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000818:Animals; D001649:Bile Duct Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D008111:Liver Function Tests; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D003598:Cytoskeletal Proteins; D015058:1-Naphthylisothiocyanate
keywords: ANIT; Cholangiofibrosis; Macrophage; Myofibroblast; Rat model