title: Attenuation of Kupffer cell function in acute on chronic liver injury enhanced engraftment of transplanted hepatocytes.
abstract: BACKGROUND
  The present study was designed to elucidate the relationship of engraftment efficiency of transplanted cells and Kupffer cell function in mice with acute on chronic liver injury and acute liver injury.
  
  
  METHODS
  The recipient dipeptidyl peptidase IV knockout (DPPIV(-/-)) mice were divided into two groups: (1) the acute on chronic liver injury group (CCl(4)/APAP group) that received CCl(4) (1 ml/kg) twice a week for 4 weeks following one dose of acetaminophen (APAP), 600 mg/kg; (2) the acute liver injury group (APAP-only group) that received a single dose of APAP at 600 mg/kg. DPPIV(+/+) hepatocytes were transplanted 24 h after APAP intoxication. Engraftment efficiency was evaluated at day 7 and day 14 after transplantation. The tumor necrosis factor-alpha (TNF-alpha) mRNA expression level of Kupffer cells immediately before cell transplantation was compared between the two groups before and after lipopolysaccharide (LPS, 100 ng/ml) stimulation.
  
  
  RESULTS
  The number of transplanted cells and clusters in each 100x microscopic field were higher in the CCl(4)/APAP group at both day 7 (21.5 +/- 6.3 versus 8.3 +/- 4.0, p < 0.001; 14.9 +/- 4.6 versus 6.6 +/- 3.4, p < 0.001, respectively) and day 14 (17.3 +/- 4.4 versus 10.2 +/- 3.3, p = 0.001; 12.6 +/- 3.2 versus 7.9 +/- 1.6, p = 0.004, respectively). After LPS stimulation, the expression level of TNF-alpha was lower (175.7 +/- 54.6 versus 465.6 +/- 64.2, p = 0.002), and the increment of TNF-alpha expression was also less significant in the CCl(4)/APAP group (1.5-fold versus 6.5-fold, p = 0.014).
  
  
  CONCLUSIONS
  Chronic liver injury desensitized Kupffer cells and reduced TNF-alpha expression, two results that correlated with the increased engraftment of transplanted cells.
authors: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Ray-Hwang
authors: RH
authors: Yuan
authors: Hui-Ling
authors: HL
authors: Chen
authors: Huey-Ling
authors: HL
authors: Chen
authors: Ming-Kung
authors: MK
authors: Hsu
authors: Po-Huang
authors: PH
authors: Lee
authors: Mei-Hwei
authors: MH
authors: Chang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000235:genetics; D022781:Hepatocytes / Q000473:pathology / Q000637:transplantation*; D007728:Kupffer Cells / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000473:pathology; D017093:Liver Failure / Q000139:chemically induced / Q000473:pathology; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000502:physiology; D051379:Mice; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018819:Dipeptidyl Peptidase 4; D017228:Hepatocyte Growth Factor; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule