Skip to main content
Top
Published in: World Journal of Surgery 6/2007

01-06-2007

Attenuation of Kupffer Cell Function in Acute on Chronic Liver Injury Enhanced Engraftment of Transplanted Hepatocytes

Authors: Ray-Hwang Yuan, Hui-Ling Chen, Huey-Ling Chen, Ming-Kung Hsu, Po-Huang Lee, Mei-Hwei Chang

Published in: World Journal of Surgery | Issue 6/2007

Login to get access

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 (CCl4/APAP group) that received CCl4 (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-α (TNF-α) 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 100× microscopic field were higher in the CCl4/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-α was lower (175.7 ± 54.6 versus 465.6 ± 64.2, p = 0.002), and the increment of TNF-α expression was also less significant in the CCl4/APAP group (1.5-fold versus 6.5-fold, p = 0.014).

Conclusions

Chronic liver injury desensitized Kupffer cells and reduced TNF-α expression, two results that correlated with the increased engraftment of transplanted cells.
Literature
1.
go back to reference Laconi S, Pillai S, Porcu PP, et al. (2001) Massive liver replacement by transplanted hepatocytes in the absence of exogenous growth stimuli in rats treated with retrorsine. Am J Pathol 158:771–777PubMed Laconi S, Pillai S, Porcu PP, et al. (2001) Massive liver replacement by transplanted hepatocytes in the absence of exogenous growth stimuli in rats treated with retrorsine. Am J Pathol 158:771–777PubMed
2.
go back to reference Laconi E, Oren R, Mukhopadhyay DK, et al. (1998) Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am J Pathol 153:319–329PubMed Laconi E, Oren R, Mukhopadhyay DK, et al. (1998) Long-term, near-total liver replacement by transplantation of isolated hepatocytes in rats treated with retrorsine. Am J Pathol 153:319–329PubMed
3.
go back to reference Lazerow SK, Abdi MS, Lewis JH (2005) Drug-induced liver disease 2004. Curr Opin Gastroenterol 21:283–292PubMedCrossRef Lazerow SK, Abdi MS, Lewis JH (2005) Drug-induced liver disease 2004. Curr Opin Gastroenterol 21:283–292PubMedCrossRef
4.
go back to reference Mitchell JR, Jollow DJ, Potter WZ, et al. (1973) Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther 187:211–217PubMed Mitchell JR, Jollow DJ, Potter WZ, et al. (1973) Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther 187:211–217PubMed
5.
go back to reference Qiu Y, Benet LZ, Burlingame AL (1998) Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry. J Biol Chem 273:17940–17953PubMedCrossRef Qiu Y, Benet LZ, Burlingame AL (1998) Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry. J Biol Chem 273:17940–17953PubMedCrossRef
6.
go back to reference Cohen SD, Khairallah EA (1997) Selective protein arylation and acetaminophen-induced hepatotoxicity. Drug Metab Rev 29:59–77PubMedCrossRef Cohen SD, Khairallah EA (1997) Selective protein arylation and acetaminophen-induced hepatotoxicity. Drug Metab Rev 29:59–77PubMedCrossRef
7.
go back to reference Michael SL, Pumford NR, Mayeux PR, et al. (1999) Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species. Hepatology 30:186–195PubMedCrossRef Michael SL, Pumford NR, Mayeux PR, et al. (1999) Pretreatment of mice with macrophage inactivators decreases acetaminophen hepatotoxicity and the formation of reactive oxygen and nitrogen species. Hepatology 30:186–195PubMedCrossRef
8.
go back to reference Nguyen TH, Mai G, Villiger P, et al. (2005) Treatment of acetaminophen-induced acute liver failure in the mouse with conditionally immortalized human hepatocytes. J Hepatol 43:1031–1037PubMedCrossRef Nguyen TH, Mai G, Villiger P, et al. (2005) Treatment of acetaminophen-induced acute liver failure in the mouse with conditionally immortalized human hepatocytes. J Hepatol 43:1031–1037PubMedCrossRef
9.
go back to reference Gupta S, Rajvanshi P, Sokhi RP, et al. (1999) Entry and integration of transplanted hepatocytes in liver plates occur by disruption of hepatic sinusoidal endothelium. Hepatology 29:509–519PubMedCrossRef Gupta S, Rajvanshi P, Sokhi RP, et al. (1999) Entry and integration of transplanted hepatocytes in liver plates occur by disruption of hepatic sinusoidal endothelium. Hepatology 29:509–519PubMedCrossRef
10.
go back to reference Gupta S, Rajvanshi P, Malhi H, et al. (2000) Cell transplantation causes loss of gap junctions and activates GGT expression permanently in host liver. Am J Physiol Gastrointest Liver Physiol 279:G815–G826PubMed Gupta S, Rajvanshi P, Malhi H, et al. (2000) Cell transplantation causes loss of gap junctions and activates GGT expression permanently in host liver. Am J Physiol Gastrointest Liver Physiol 279:G815–G826PubMed
11.
go back to reference Slehria S, Rajvanshi P, Ito Y, et al. (2002) Hepatic sinusoidal vasodilators improve transplanted cell engraftment and ameliorate microcirculatory perturbations in the liver. Hepatology 35:1320–1328PubMedCrossRef Slehria S, Rajvanshi P, Ito Y, et al. (2002) Hepatic sinusoidal vasodilators improve transplanted cell engraftment and ameliorate microcirculatory perturbations in the liver. Hepatology 35:1320–1328PubMedCrossRef
12.
go back to reference Lemasters JJ, Thurman RG (1997) Reperfusion injury after liver preservation for transplantation. Annu Rev Pharmacol Toxicol 37:327–338PubMedCrossRef Lemasters JJ, Thurman RG (1997) Reperfusion injury after liver preservation for transplantation. Annu Rev Pharmacol Toxicol 37:327–338PubMedCrossRef
13.
go back to reference Serracino-Inglott F, Habib NA, Mathie RT (2001) Hepatic ischemia-reperfusion injury. Am J Surg 181:160–166PubMedCrossRef Serracino-Inglott F, Habib NA, Mathie RT (2001) Hepatic ischemia-reperfusion injury. Am J Surg 181:160–166PubMedCrossRef
14.
go back to reference Luckey SW, Petersen DR (2001) Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. Exp Mol Pathol 71:226–240PubMedCrossRef Luckey SW, Petersen DR (2001) Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. Exp Mol Pathol 71:226–240PubMedCrossRef
15.
go back to reference Blazka ME, Wilmer JL, Holladay SD, et al. (1995) Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 13:43–52CrossRef Blazka ME, Wilmer JL, Holladay SD, et al. (1995) Role of proinflammatory cytokines in acetaminophen hepatotoxicity. Toxicol Appl Pharmacol 13:43–52CrossRef
16.
go back to reference Bruccoleri A, Gallucci R, Germolec DR, et al. (1997) Induction of early-immediate genes by tumor necrosis factor-α contributes to liver repair following chemical-induced hepatotoxicity. Hepatology 25:133–140PubMedCrossRef Bruccoleri A, Gallucci R, Germolec DR, et al. (1997) Induction of early-immediate genes by tumor necrosis factor-α contributes to liver repair following chemical-induced hepatotoxicity. Hepatology 25:133–140PubMedCrossRef
17.
go back to reference Yuan RH, Ogawa A, Ogawa E, et al. (2003) p27Kip1 inactivation provides a proliferative advantage to transplanted hepatocytes in DPPIV/Rag2 double knockout mice after repeated host liver injury. Cell Transplant 12:907–919PubMed Yuan RH, Ogawa A, Ogawa E, et al. (2003) p27Kip1 inactivation provides a proliferative advantage to transplanted hepatocytes in DPPIV/Rag2 double knockout mice after repeated host liver injury. Cell Transplant 12:907–919PubMed
18.
go back to reference Mathew J, Hines JE, Toole K, et al. (1994) Quantitative analysis of macrophages and perisinusoidal cells in primary biliary cirrhosis. Histopathology 25:65–70PubMedCrossRef Mathew J, Hines JE, Toole K, et al. (1994) Quantitative analysis of macrophages and perisinusoidal cells in primary biliary cirrhosis. Histopathology 25:65–70PubMedCrossRef
19.
go back to reference Micklen K, Rigney E, Cordell J, et al. (1989) A human macrophage-associated antigen (CD68) detected by six different monoclonal antibodies. Br J Haematol 73:6–11 Micklen K, Rigney E, Cordell J, et al. (1989) A human macrophage-associated antigen (CD68) detected by six different monoclonal antibodies. Br J Haematol 73:6–11
20.
go back to reference Brown KE, Brunt EM, Heinecke JW (2001) Immunohistochemical detection of myeloperoxidase and its oxidation products in Kupffer cells of human liver. Am J Pathol 159:2081–2088PubMed Brown KE, Brunt EM, Heinecke JW (2001) Immunohistochemical detection of myeloperoxidase and its oxidation products in Kupffer cells of human liver. Am J Pathol 159:2081–2088PubMed
21.
go back to reference Su GL, Klein RD, Aminlari A, et al. (2000) Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4. Hepatology 31:932–936PubMedCrossRef Su GL, Klein RD, Aminlari A, et al. (2000) Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4. Hepatology 31:932–936PubMedCrossRef
22.
go back to reference Yuan RH, Jeng YM, Chen HL, et al. (2005) Opposite roles of human PAP and REG1A expression in hepatocellular carcinoma (HCC): association of PAP expression with low-stage HCC, β-catenin mutation, and favorable prognosis. Clin Cancer Res 11:2568–2575PubMedCrossRef Yuan RH, Jeng YM, Chen HL, et al. (2005) Opposite roles of human PAP and REG1A expression in hepatocellular carcinoma (HCC): association of PAP expression with low-stage HCC, β-catenin mutation, and favorable prognosis. Clin Cancer Res 11:2568–2575PubMedCrossRef
23.
go back to reference Nagayama T, Nagayama M, Kohara S, et al. (2004) Post-ischemic delayed expression of hepatocyte growth factor and c-Met in mouse brain following focal cerebral ischemia. Brain Res 999:155–166PubMedCrossRef Nagayama T, Nagayama M, Kohara S, et al. (2004) Post-ischemic delayed expression of hepatocyte growth factor and c-Met in mouse brain following focal cerebral ischemia. Brain Res 999:155–166PubMedCrossRef
24.
go back to reference Gujral JS, Knight TR, Farhood A, et al. (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicol Sci 67:322–328PubMedCrossRef Gujral JS, Knight TR, Farhood A, et al. (2002) Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicol Sci 67:322–328PubMedCrossRef
25.
go back to reference Crofton RW, Diesselhoff-den Dulk MM, Van Furth R (1978) The origin, kinetics and characteristics of the Kupffer cells in the normal steady state. J Exp Med 148:1–17PubMedCrossRef Crofton RW, Diesselhoff-den Dulk MM, Van Furth R (1978) The origin, kinetics and characteristics of the Kupffer cells in the normal steady state. J Exp Med 148:1–17PubMedCrossRef
26.
go back to reference Joseph B, Malhi H, Bhargava KK, et al. (2002) Kupffer cells participate in early clearance of syngeneic hepatocytes transplanted in the rat liver. Gastroenterology 123:1677–1685PubMedCrossRef Joseph B, Malhi H, Bhargava KK, et al. (2002) Kupffer cells participate in early clearance of syngeneic hepatocytes transplanted in the rat liver. Gastroenterology 123:1677–1685PubMedCrossRef
27.
go back to reference Fukuda M, Yokoyama H, Mizukami T, et al. (2004) Kupffer cell depletion attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide treatment. J Gastroenterol Hepatol 19:1155–1162PubMedCrossRef Fukuda M, Yokoyama H, Mizukami T, et al. (2004) Kupffer cell depletion attenuates superoxide anion release into the hepatic sinusoids after lipopolysaccharide treatment. J Gastroenterol Hepatol 19:1155–1162PubMedCrossRef
28.
go back to reference Ishizaki-Koizumi S, Sonaka I, Takei Y, et al. (2004) The glycine analogue, aminomethanesulfonic acid, inhibits LPS-induced production of TNF-alpha in isolated rat Kupffer cells and exerts hepatoprotective effects in mice. Biochem Biophys Res Commun 322:514–519PubMedCrossRef Ishizaki-Koizumi S, Sonaka I, Takei Y, et al. (2004) The glycine analogue, aminomethanesulfonic acid, inhibits LPS-induced production of TNF-alpha in isolated rat Kupffer cells and exerts hepatoprotective effects in mice. Biochem Biophys Res Commun 322:514–519PubMedCrossRef
29.
go back to reference Barshes NR, Wyllie S, Goss JA (2005) Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. J Leukocyte Biol 77:587–597PubMedCrossRef Barshes NR, Wyllie S, Goss JA (2005) Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts. J Leukocyte Biol 77:587–597PubMedCrossRef
30.
go back to reference Bottino R, Fernandez LA, Ricordi C, et al. (1988) Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation. Diabetes 47:316–323CrossRef Bottino R, Fernandez LA, Ricordi C, et al. (1988) Transplantation of allogeneic islets of Langerhans in the rat liver: effects of macrophage depletion on graft survival and microenvironment activation. Diabetes 47:316–323CrossRef
31.
go back to reference Laskin DL, Pendino KJ (1995) Macrophages and inflammatory mediators in tissue injury. Annu Rev Pharmacol Toxicol 35:655–677PubMedCrossRef Laskin DL, Pendino KJ (1995) Macrophages and inflammatory mediators in tissue injury. Annu Rev Pharmacol Toxicol 35:655–677PubMedCrossRef
32.
go back to reference Ito Y, Bethea NW, Abril ER, et al. (2003) Early hepatic microvascular injury in response to acetaminophen toxicity. Microcirculation 10:391–400PubMedCrossRef Ito Y, Bethea NW, Abril ER, et al. (2003) Early hepatic microvascular injury in response to acetaminophen toxicity. Microcirculation 10:391–400PubMedCrossRef
34.
go back to reference Kaido T, Imamura M (2001) Hepatocyte growth factor: clinical implications in hepatobiliary pancreatic surgery. J Hepatobiliary Pancreat Surg 8:65–75PubMedCrossRef Kaido T, Imamura M (2001) Hepatocyte growth factor: clinical implications in hepatobiliary pancreatic surgery. J Hepatobiliary Pancreat Surg 8:65–75PubMedCrossRef
35.
go back to reference Matsumoto K, Nakamura T (1991) Hepatocyte growth factor: molecular structure and implications for a central role in liver regeneration. J Gastroenterol Hepatol 6:509–519PubMed Matsumoto K, Nakamura T (1991) Hepatocyte growth factor: molecular structure and implications for a central role in liver regeneration. J Gastroenterol Hepatol 6:509–519PubMed
Metadata
Title
Attenuation of Kupffer Cell Function in Acute on Chronic Liver Injury Enhanced Engraftment of Transplanted Hepatocytes
Authors
Ray-Hwang Yuan
Hui-Ling Chen
Huey-Ling Chen
Ming-Kung Hsu
Po-Huang Lee
Mei-Hwei Chang
Publication date
01-06-2007
Publisher
Springer-Verlag
Published in
World Journal of Surgery / Issue 6/2007
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-007-9044-0

Other articles of this Issue 6/2007

World Journal of Surgery 6/2007 Go to the issue