Scavenger receptor-like receptors for the binding of lipopolysaccharide and lipoteichoic acid to liver endothelial and Kupffer cells

Abstract

This study was undertaken to identify the role of scavenger receptors in the catabolism of lipopolysaccharide (LPS) and lipoteichoic acid (LTA). LPS is mainly cleared from the blood by the liver. The Kupffer cells are primarily responsible for this clearance. Although several binding sites have been described for LPS and LTA, only CD14 is involved in LPS signalling. Scavenger receptor type A (SR-A) is expressed in the liver on endothelial cells and Kupffer cells, and macrosialin (class D scavenger receptor) is expressed on Kupffer cells. Fucoidin and poly-I are both good inhibitors of scavenger receptors. Fucoidin significantly reduced the serum clearance of [¹²⁵I]-LPS and decreased liver uptake of [¹²⁵I]-LPS by ~40%. Poly-I inhibited the binding of [¹²⁵I]-LPS to isolated Kupffer and endothelial cells by 75%, while poly-A, a polyanionic substrate that does not block scavenger receptors, had no effect. LPS significantly inhibited the binding of acetylated LDL and oxidized LDL (two well-described scavenger receptor ligands) to isolated Kupffer and liver endothelial cells. OxLDL and acLDL did not affect the binding of LPS to these cells. We conclude that on both endothelial cells and Kupffer cells, LPS mainly binds to scavenger receptors, but SR-A and macrosialin contribute to a limited extent to the binding of LPS. Injection of LTA into C57Bl6 mice resulted in a maximal liver uptake of 20% of the injected dose. In the liver, 50% was bound by the Kupffer cells, 20% by parenchymal cells and 30% by liver endothelial cells. The contribution of SR-A to the plasma clearance of LTA was limited. A main component in the catabolism of LTA is the interaction of LTA with plasma lipoproteins, which limit the uptake of LTA by tissues and extend the plasma half-life of LTA.

References

Bates DW , Pruess KE , Lee TH How bad are bacteremia and sepsis? Outcomes in a cohort with suspected bacteremia . Arch Intern Med 1995; 155: 593—598.

Cleveland MG , Gorham JD , Murphy TL , Tuomanen E. , Murphy KM Lipoteichoic acid preparations of Gram-positive bacteria induce interleukin-12 through a CD14-dependent pathway. Infect Immun 1996; 64: 1906—1912.

Terpstra V. , van Amersfoort ES , van Velzen AG , Kuiper J. , van Berkel ThJC. Hepatic and extrahepatic scavenger receptors: function in relation to disease . Arterioscler Thromb Vasc Biol 2000; 20: 1860—1872.

Shnyra A. , Lindberg AA Scavenger receptor pathway for lipopolysaccharide binding to Kupffer and endothelial liver cells in vitro. Infect Immun 1995; 63: 865—873.

Hampton RY , Golenbock DT , Penman M. , Krieger M. , Raetz Crh. Recognition and plasma clearance of endotoxin by scavenger receptors. Nature 1991; 352: 342—352.

Haworth R. , Platt N. , Keshav S. et al. The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal endotoxic shock. J Exp Med 1997; 186: 1431—1439.

de Rijke YB , van Berkel ThJC. Rat liver Kupffer and endothelial cells express different binding proteins for modified low density lipoproteins. J Biol Chem 1994; 269: 824—827.

Ingalls RR , Golenbock DT CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J Exp Med 1995; 181: 1473—1479.

Parent JB Membrane receptors on rat hepatocytes for the inner core region of bacterial lipopolysaccharide. J Biol Chem 1990; 265: 3455—3461.

10.

Ulevitch RJ The preparation and characterization of a radioiodinated bacterial lipopolysaccharide. Immunochemistry 1978; 15: 157—164.

11.

Kuiper J. , Bakkeren HF , Biessen Eal , van Berkel ThJC. Characterisation of the interaction of galactose-terminated particles with rat Kupffer cells. Biochem J 1994; 299: 285—290.

12.

Suzuki H. , Kurihara Y. , Takeya M. et al. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 1997 ; 386: 292—296.