title: Oval cell response is attenuated by depletion of liver resident macrophages in the 2-AAF/partial hepatectomy rat.
abstract: OBJECTIVE
  Macrophages are known to play an important role in hepatocyte mediated liver regeneration by secreting inflammatory mediators. However, there is little information available on the role of resident macrophages in oval cell mediated liver regeneration. In the present study we aimed to investigate the role of macrophages in oval cell expansion induced by 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) in rats.
  
  
  RESULTS
  We depleted macrophages in the liver of 2-AAF/PH treated rats by injecting liposome encapsulated clodronate 48 hours before PH. Regeneration of remnant liver mass, as well as proliferation and differentiation of oval cells were measured. We found that macrophage-depleted rats suffered higher mortality and liver transaminase levels. We also showed that depletion of macrophages yielded a significant decrease of EPCAM and PCK positive oval cells in immunohistochemical stained liver sections 9 days after PH. Meanwhile, oval cell differentiation was also attenuated as a result of macrophage depletion, as large foci of small basophilic hepatocytes were observed by day 9 following hepatectomy in control rats whereas they were almost absent in macrophage depleted rats. Accordingly, real-time polymerase chain reaction analysis showed lower expression of albumin mRNA in macrophage depleted livers. Then we assessed whether macrophage depletion may affect hepatic production of stimulating cytokines for liver regeneration. We showed that macrophage-depletion significantly inhibited hepatic expression of tumor necrosis factor-α and interleukin-6, along with a lack of signal transducer and activator of transcription 3 phosphorylation during the early period following hepatectomy.
  
  
  CONCLUSIONS
  These data indicate that macrophages play an important role in oval cell mediated liver regeneration in the 2-AAF/PH model.
authors.affiliation: Hepatic Surgery Centre, Huazhong University of Science and Technology, Tongji Hospital, Wuhan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Xiang
authors.forename: Han-Hua
authors.initials: HH
authors.lastname: Dong
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Liang
authors.forename: Song-Qing
authors.initials: SQ
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Li
authors.forename: Bi-Xiang
authors.initials: BX
authors.lastname: Zhang
authors.forename: Bin-Hao
authors.initials: BH
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Jing
authors.forename: Stephen
authors.initials: S
authors.lastname: Tomlinson
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
mesh_terms: D015073:2-Acetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006498:Hepatectomy / Q000009:adverse effects*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008081:Liposomes / Q000378:metabolism; D008115:Liver Regeneration / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D008081:Liposomes; D015073:2-Acetylaminofluorene