BACKGROUND: Macrophages undergo maladaptive alterations after trauma. In this study, we assessed the role of Kupffer cells in hepatic microcirculatory response to endothelin-1 (ET-1) after femur fracture (FFx) and cecal ligation and puncture (CLP). METHODS: Sprague-Dawley rats (200-300 g) underwent sham, FFx, CLP, or FFx + CLP. To ablate Kupffer cells, group 1 animals were treated with gadolinium chloride, and group 2 animals received saline. Hepatic microcirculation was assessed by intravital microscopy. Liver mitochondrial redox state and tissue oxygen (tPo2) were determined by NADH and ruthenium fluorescence, respectively. Liver damage was estimated by alanine aminotransferase levels. Differences were assessed using analysis of variance followed by Student-Newman-Keuls post hoc test. RESULTS: After 10 minutes of ET-1, CLP and FFx + CLP caused significant reduction in hepatic perfusion index (2.5-fold and 5-fold vs. sham, p < 0.05, respectively), redox state (36% and 45% vs. sham, p < 0.01, respectively), tPo2 (10% and 12% vs. sham, p < 0.05, respectively), and more liver damage compared with sham and FFx-treated animals. Kupffer cell depletion restored microcirculation, redox state, and tPo2 and abrogated hepatocellular damage. CONCLUSION: Kupffer cells contribute directly to hepatic microcirculatory dysfunction and liver injury after inflammatory stress. Furthermore, Kupffer cell depletion ameliorates the microcirculatory perturbations of trauma and sepsis. Thus, modulation of Kupffer cell response may prove beneficial.
BACKGROUND: Macrophages undergo maladaptive alterations after trauma. In this study, we assessed the role of Kupffer cells in hepatic microcirculatory response to endothelin-1 (ET-1) after femur fracture (FFx) and cecal ligation and puncture (CLP). METHODS:Sprague-Dawley rats (200-300 g) underwent sham, FFx, CLP, or FFx + CLP. To ablate Kupffer cells, group 1 animals were treated with gadolinium chloride, and group 2 animals received saline. Hepatic microcirculation was assessed by intravital microscopy. Liver mitochondrial redox state and tissue oxygen (tPo2) were determined by NADH and ruthenium fluorescence, respectively. Liver damage was estimated by alanine aminotransferase levels. Differences were assessed using analysis of variance followed by Student-Newman-Keuls post hoc test. RESULTS: After 10 minutes of ET-1, CLP and FFx + CLP caused significant reduction in hepatic perfusion index (2.5-fold and 5-fold vs. sham, p < 0.05, respectively), redox state (36% and 45% vs. sham, p < 0.01, respectively), tPo2 (10% and 12% vs. sham, p < 0.05, respectively), and more liver damage compared with sham and FFx-treated animals. Kupffer cell depletion restored microcirculation, redox state, and tPo2 and abrogated hepatocellular damage. CONCLUSION: Kupffer cells contribute directly to hepatic microcirculatory dysfunction and liver injury after inflammatory stress. Furthermore, Kupffer cell depletion ameliorates the microcirculatory perturbations of trauma and sepsis. Thus, modulation of Kupffer cell response may prove beneficial.
Authors: Willson Kwok; Sang Ho Lee; Cathy Culberson; Katarzyna Korneszczuk; Mark G Clemens Journal: Am J Physiol Gastrointest Liver Physiol Date: 2009-11 Impact factor: 4.052
Authors: Hendrik Freise; Fritz Daudel; Christina Grosserichter; Stefan Lauer; Juergen Hinkelmann; Hugo K Van Aken; Andreas W Sielenkaemper; Martin Westphal; Lars G Fischer Journal: Crit Care Date: 2009-07-13 Impact factor: 9.097