Kinetics of lipopolysaccharide clearance by Kupffer and parenchyma cells in perfused rat liver

Anwar B. Bikhazi, Abdo R. Jurjus, Maud T. Kamal, Ali M. Al-Housseini, Rola N. Saab, Wael A. Jaroudi, Khalil M. Bitar

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 (GdCl3) 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, GdCl3-treated rats, and colchicine plus GdCl3-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 GdCl3-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 GdCl3 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.

Original languageEnglish (US)
Pages (from-to)339-348
Number of pages10
JournalComparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
Volume129
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Binding
  • Colchicine
  • Endocytosis
  • Gadolinium chloride
  • Influx
  • Liver

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

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