Emergence of Different Macrophage Populations in Hepatic Fibrosis Following Thioacetamide-induced Acute Hepatocyte Injury in Rats

Ide, Mika; Yamate, Jyoji; Machida, Yuuko; Nakanishi, Masayoshi; Kuwamura, Mitsuru; Kotani, Takao; Sawamoto, Osamu

doi:10.1053/jcpa.2002.0603

Cited by 48 publications

(42 citation statements)

References 38 publications

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“…The methods have been described elsewhere (Yamate et al, 2002a;Ide et al, 2003). Briefly, after pretreatments applied for each primary antibody (Table 1) to inactivate endogenous peroxidase, the deparaffinized sections were treated with 5% skimmed milk for 30 minutes, and incubated with each primary antibody for 14-24 hours.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

Cisplatin-Induced Renal Interstitial Fibrosis in Neonatal Rats, Developing as Solitary Nephron Unit Lesions

et al. 2005

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Cisplatin (CDDP)-induced renal lesions in rats prove a useful model for analysis of the pathogenesis of post-tubular injury-renal interstitial fibrosis. This study investigated the histopathological changes in 10-day-old neonatal rats induced by a single injection of CDDP (4.5 mg/kg). Compared with age-matched controls, on postinjection (PI) days 1 to 6, the number of apoptotic cells, demonstrable with TUNEL method, was significantly increased in CDDP-treated neonates, and there was no marked epithelial necrosis nor fibrotic lesions. Fibrotic lesions began to be developed solitarily around some nephrons with dilated ducts in the corticomedullary junction on PI day 10 and the lesions became more prominent until PI day 20. The α-SMA-positive myofibroblastic cells were seen exclusively in the fibrotic lesions. Additionally, the numbers of macrophages reacting with ED1 (specific for exudate macrophages), ED2 (for resident macrophages), and OX6 (recognizing MHC class II antigens expressed in antigen-presenting macrophages/dendritic cells) were significantly increased around the affected renal tubules. A greater immunoreaction for TGF-β1 was seen mostly in the renal epithelial cells of CDDP-treated neonates. These findings indicated that macrophage populations and myofibrolastic cells as well as TGF-β1 may be responsible for the production of neonatal renal interstitial fibrosis. Compared with CDDP-injected adult rats that develop extensive interstitial fibrosis (Yamate et al., J Comp Pathol, 1995), the formation of fibrotic lesions was delayed, and the lesions were limited to the area around the affected nephrons; this could be attributable to differences in renal morphology between neonates and mature kidney of adult rats.

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Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

Cisplatin-Induced Renal Interstitial Fibrosis in Neonatal Rats, Developing as Solitary Nephron Unit Lesions

et al. 2005

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“…Myofibroblasts are capable of producing collagens, resulting in fibrosis. 15,17,21,45 Similar to human cases, a-SMAþ myofibroblasts were found in sclerotic dermis. 15,30,33 In addition to exudative macrophages, macrophages reacting to CD163 were increased in BLM-injected skin, showing similar kinetics to that of CD68þ cells.…”

Section: Discussionmentioning

confidence: 55%

“…8,45,46 It is well known that myofibroblasts, which are contractile cells, are induced by TGF-b1. 15,17,21 These findings indicated that CD68þ cells might be responsible for myofibroblast induction through increased production of TGF-b1. 42 Consequently, the a-SMAþ myofibroblasts were gradually increased throughout the observation period in BLM-injected skin.…”

Section: Discussionmentioning

confidence: 89%

“…2,25,44 It has been suggested that factors released from inflammatory cells in the early stages lead to the formation of myofibroblasts capable of producing collagens, resulting in fibrosis. 15,17,21,27,45 In particular, macrophages are thought to act as important cells for the onset of scleroderma. 13,22 Recruitment of macrophages into injured areas is mediated by chemokines such as monocyte chemoattractant protein-1 (MCP-1) and colony-stimulating factor-1 (CSF-1).…”

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confidence: 99%

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Immunophenotypical Characterization of Macrophages in Rat Bleomycin-Induced Scleroderma

et al. 2012

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Scleroderma is a skin disorder characterized by persistent fibrosis. Macrophage properties influencing cutaneous fibrogenesis remain to be fully elucidated. In this rat (F344 rats) model of scleroderma, at 1, 2, 3, and 4 weeks after initiation of daily subcutaneous injections of bleomycin (BLM; 100 ml of 1 mg/ml daily), skin samples were collected for histological and immunohistochemical evaluations. Immunohistochemically, the numbers of cells reacting to ED1 (anti-CD68; phagocytic activity) and ED2 (anti-CD163; inflammatory factor production) began to increase at week 1, peaked at week 2, and decreased thereafter. In contrast, the increased number of cells reacting to OX6 (anti-MHC class II molecules) was seen from week 2 and remained elevated until week 4. aSmooth muscle actin-positive myofibroblasts were increased for 4 weeks. Double labeling revealed that galectin-3, a regulator of fibrogenic factor TGF-b1, was expressed in CD68þ, CD163þ, and MHC class IIþ macrophages and myofibroblasts. mRNA expression of TGF-b1, as well as MCP-1 and CSF-1 (both macrophage function modulators), were significantly elevated at weeks 1 to 4. This study shows that the increased number of macrophages with heterogeneous immunophenotypes, which might be induced by MCP-1 and CSF-1, could participate in the sclerotic lesion formation, presumably through increased fibrogenic factors such as galectin-3 and TGF-b1; the data may provide useful information to understand the pathogenesis of the human scleroderma condition.

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“…Further knowledge was gathered by looking for mechanistic data of other chemicals which are known inducers of liver fibrosis, namely Thioacetamide (Akhtar and Nadeem Sheikh, 2013;Altomonte et al, 2013;Amin al., 2013;Chilakapati et al, 2005;Hajovsky et al, 2012;Ide et al, 2003;Kang, 2008;Kim et al, 2013;Ledda-Columbano et al, 1991;Low et al, 2004;Nafees et al, 2013;Sarma et al, 2012;Shirai et al, 2013;Staňková et al, 2010;Sun et al, 2000;Waters et al, 2005), Amiodarone (Cimic and Sirintrapun, 2013;Felser et al, 2013;Golli-Bennour et al, 2012;Isomoto et al, 2004;Kicker et al, 2012;Lu et al, 2013: Nasser et al, 2013, Methotrexate (AlAli et al, 2005;Al-Motabagani, 2006;Belinsky et al, 2007;Fathi et al, 2002;Hall et al, 1991;Hytiroglou et al, 2004;Lindsay K et al, 2009), Isoniazid (Bhadauria et al, 2007;Schwab and Tuschl, 2003;Singh et al, 2010;Tostmann et al, 2008), Dimethyl Nitrosamine (George et al, 2003;George, 2001;Ju et al, 2013;Usunomena et al, 2012), Ethanol (Das et al, 2010;…”

Section: Uncertainties Inconsistencies and Data Gapsmentioning

confidence: 99%

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis

Landesmann

2016

OECD Series on Adverse Outcome Pathways

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Emergence of Different Macrophage Populations in Hepatic Fibrosis Following Thioacetamide-induced Acute Hepatocyte Injury in Rats

Cited by 48 publications

References 38 publications

Cisplatin-Induced Renal Interstitial Fibrosis in Neonatal Rats, Developing as Solitary Nephron Unit Lesions

Cisplatin-Induced Renal Interstitial Fibrosis in Neonatal Rats, Developing as Solitary Nephron Unit Lesions

Immunophenotypical Characterization of Macrophages in Rat Bleomycin-Induced Scleroderma

Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis

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