Attenuation of Kupffer cell function in acute on chronic liver injury enhanced engraftment of transplanted hepatocytes

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-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 100 x 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-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 CCl4/ 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.