title: Participation of functionally different macrophage populations and monocyte chemoattractant protein-1 in early stages of thioacetamide-induced rat hepatic injury.
abstract: Macrophages are crucial in hepatic fibrogenesis. In acute hepatic necrosis induced in rats by a single injection of 300 mg/kg body weight (BW) of thioacetamide (TAA), macrophage properties were investigated using single or double immunohistochemistry. Macrophages reacting with anti-CD68, anti-CD163, or major histocompatibility complex (anti-MHC) class II antibody appeared in injured centrilobular areas on days 1-5 after injection. Increased expression of CD68 and CD163 reflect phagocytosis and production of pro-inflammatory factors, respectively. There were also macrophages double-positive to CD68/CD163, CD68/MHC class II, or CD163/MHC class II; of these, macrophages double-positive to CD68/MHC class II were most frequent, indicating that macrophages with enhanced phagocytic activity came to express MHC class II. The appearance of these macrophages corresponded to increased expression of mRNAs of monocyte chemoattractant protein-1 (MCP-1), a chemokine, on day 1, and TGF-beta1, a fibrogenic factor, on day 3. Some hepatic stellate cells (HSCs) in injured areas reacted with anti-MCP-1 antibody. To investigate the effects of MCP-1, we added MCP-1 to HS-P, a rat macrophage line. Addition of MCP-1 increased immunoexpression for CD68 and CD163 and up-regulated TGF-beta1 mRNA expression. Collectively, macrophages in acute hepatic necrosis may express different properties such as phagocytosis, MHC class II expression, and TGF-beta1 production; such expression may be influenced by MCP-1 produced by HSCs.
authors.affiliation: Laboratories of Veterinary Pathology and Molecular Science, Life and Environmental Sciences, Osaka Prefecture University, Nakaku, Sakai, Osaka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takenaka
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kuwamura
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000378:metabolism; D013853:Thioacetamide / Q000008:administration & dosage / Q000633:toxicity*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D000949:Histocompatibility Antigens Class II; D011956:Receptors, Cell Surface; D013853:Thioacetamide; D053773:Transforming Growth Factor beta1; D000098902:CD163 Antigen; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C459465:OX-62 antigen, rat