Kinetics of lipopolysaccharide clearance by Kupffer and parenchyma cells in perfused rat liver.
We studied the kinetics of [3H]lipopolysaccharide ([3H]LPS) (endotoxin) binding to Kupffer cells and hepatocytes at the level of the microtubular system after treatment with gadolinium chloride (GdCl(3)) and colchicine. Liver perfusion in Sprague-Dawley rats involves both portal vein and thoracic inferior vena cava cannulations as inlet and outlet, respectively. The subhepatic inferior vena cava is ligated to prevent perfusate leakage. Buffer containing 2% serum and [3H]LPS is administered at 1 ml/min and collected for 50 min. Rate constants for hepatocellular clearance of [3H]LPS in controls, colchicine-treated rats, GdCl(3)-treated rats, and colchicine plus GdCl(3)-treated rats are assessed using a simplified mathematical model. Forward-binding, reversal-binding, residency time, and influx rate constants are estimated. Results show that in GdCl(3)-treated rats, the hepatocytes effectively clear endotoxin from the circulation, and its ultimate binding affinity at the hepatocyte site is somewhat reduced compared to the Kupffer cells. In colchicine-treated rats, the disruption of the microtubule network altered [3H]LPS binding with Kupffer cells, suggesting that the microfilament-microtubular network also affects Kupffer cell function. Simultaneous treatments with colchicine and GdCl(3) increased the influx rate constant, suggesting that the compiled morphological alterations up-regulated endotoxin clearance by the liver, as indicated by a drastic increase in cellular vacuolation. In conclusion, the kinetics of the trafficking process of [3H]LPS clearance are regulated by apical-sinusoidal endocytotic and canalicular routes.
Bikhazi
A B
AB
Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. ab04@aub.edu.lb
Jurjus
A R
AR
Kamal
M T
MT
Al-Housseini
A M
AM
Saab
R N
RN
Jaroudi
W A
WA
Bitar
K M
KM
D000818:Animals; D001665:Binding Sites; D003078:Colchicine / Q000494:pharmacology; D004731:Endotoxins / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000494:pharmacology; D022781:Hepatocytes; D007700:Kinetics; D007728:Kupffer Cells / Q000502:physiology*; D008070:Lipopolysaccharides / Q000493:pharmacokinetics*; D008099:Liver / Q000502:physiology*; D008870:Microtubules / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D004731:Endotoxins; D008070:Lipopolysaccharides; D005682:Gadolinium; C038958:gadolinium chloride; D003078:Colchicine