Attenuation of kupffer cell function in acute on chronic liver injury enhanced engraftment of transplanted hepatocytes
Journal
World Journal of Surgery
Journal Volume
31
Journal Issue
6
Pages
1270-1277
Date Issued
2007
Author(s)
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 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. ? 2007 Soci?t? Internationale de Chirurgie.
SDGs
Other Subjects
dipeptidyl peptidase IV; lipopolysaccharide; messenger RNA; paracetamol; tumor necrosis factor alpha; animal experiment; animal model; animal tissue; article; cell transplantation; controlled study; engraftment; Kupffer cell; liver cell; liver injury; microscope; mouse; nonhuman; statistical significance; surgical technique; Animals; Antigens, CD; Antigens, CD26; Antigens, Differentiation, Myelomonocytic; Cell Division; Cell Survival; Hepatitis, Toxic; Hepatocyte Growth Factor; Hepatocytes; Kupffer Cells; Lipopolysaccharides; Liver; Liver Failure; Liver Function Tests; Liver Regeneration; Mice; Microscopy, Fluorescence; RNA, Messenger; Tumor Necrosis Factor-alpha
Type
journal article