title: Effects of gadolinium chloride (GdCl(3)) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions.
abstract: Macrophages infiltrating injured tissue play an important part in fibrogenesis. To shed light on the functional roles of macrophages, we investigated the appearance of macrophage populations in thioacetamide (TAA)-induced rat hepatic lesions, with or without pretreatment with GdCl(3), a chemical capable of inhibiting Kupffer cell functions. In the GdCl(3)+TAA group rats received a single intraperitoneal injection of GdCl(3) (7.5mg/kg body weight) and, after 24h, a single intravenous injection of TAA (300mg/kg body weight). Rats in the TAA group received TAA only. Rats in both groups were examined on post-TAA injection (PTI) days 3, 5, and 7. In the TAA group, on PTI day 3, when TAA-induced hepatocyte injury was particularly prominent, the number of macrophages peaked, subsequently decreasing until PTI day 7. As compared with the TAA group, the GdCl(3)+TAA group showed significantly decreased numbers of ED1-immunolabelled cells (exudate macrophages) and ED2-immunolabelled cells (Kupffer cells) on PTI days 3, 5, and 7, and OX6-immunolabelled cells (antigen-presenting macrophages) on PTI days 3 and 5. Although less strikingly, the numbers of alpha-smooth muscle actin-positive myofibroblasts and fibrotic areas were decreased in the GdCl(3)+TAA group. By RT-PCR, the expression of TGF-beta1 mRNA was suppressed on PTI days 3 and 7 in the GdCl(3)+TAA group, and the suppressed expression was confirmed in vitro by treating rat macrophage-like cells (HS-P) with 1% GdCl(3). The study showed that GdCl(3) treatment decreased the numbers of macrophages appearing in hepatic lesions and inhibited TGF-beta1 mRNA expression in macrophages. Decreased numbers of macrophages may contribute to improvement of hepatic fibrosis.
authors.affiliation: Laboratory of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ide
authors.forename: M
authors.initials: M
authors.lastname: Kuwamura
authors.forename: T
authors.initials: T
authors.lastname: Kotani
authors.forename: O
authors.initials: O
authors.lastname: Sawamoto
authors.forename: J
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005682:Gadolinium / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013853:Thioacetamide / Q000633:toxicity*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D013853:Thioacetamide; D005682:Gadolinium; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C038958:gadolinium chloride