title: Kinetics of lipopolysaccharide clearance by Kupffer and parenchyma cells in perfused rat liver.
abstract: 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.
authors.affiliation: Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. ab04@aub.edu.lb
authors.forename: A B
authors.initials: AB
authors.lastname: Bikhazi
authors.forename: A R
authors.initials: AR
authors.lastname: Jurjus
authors.forename: M T
authors.initials: MT
authors.lastname: Kamal
authors.forename: A M
authors.initials: AM
authors.lastname: Al-Housseini
authors.forename: R N
authors.initials: RN
authors.lastname: Saab
authors.forename: W A
authors.initials: WA
authors.lastname: Jaroudi
authors.forename: K M
authors.initials: KM
authors.lastname: Bitar
mesh_terms: 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
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D005682:Gadolinium; C038958:gadolinium chloride; D003078:Colchicine