Kupffer cell ablation improves hepatic microcirculation after trauma and sepsis.
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.


CONCLUSIONS
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.
Keller
Steve A
SA
F.H. "Sammy" Ross Jr. Trauma Center, Department of Surgery, Carolinas Medical Center, University of North Carolina at Charlotte, Charlotte, North Carolina, USA.
Paxian
Marcus
M
Ashburn
Jeanie H
JH
Clemens
Mark G
MG
Huynh
Toan
T
D000818:Animals; D002432:Cecum / Q000293:injuries; D019332:Endothelin-1 / Q000494:pharmacology; D005264:Femoral Fractures / Q000503:physiopathology*; D005296:Ferrous Compounds; D007728:Kupffer Cells / Q000502:physiology*; D008026:Ligation; D008099:Liver / Q000098:blood supply*; D008102:Liver Circulation / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009243:NAD / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*
D019332:Endothelin-1; D005296:Ferrous Compounds; D009243:NAD; C020748:ferrous sulfate