Identification of receptors for lipopolysaccharide on liver endothelial and Kupffer cells

Lipopolysaccharide (LPS) binds to a scala of receptors on different cell types. LPS binding sites on endothelial cells or macrophages described are: CD11/CD18, CD14, which binds a complex of LPS and LPS binding protein (LBP), and scavenger receptors. We investigated the role of scavenger receptors in the binding of LPS to liver endothelial and Kupffer cells in vivo and in vitro. Fucoidin, a scavenger receptor inhibitor, significantly inhibited the serum decay of I-125-LPS and decreased the liver uptake of I-125-LPS for about 40%. Binding of I-125-LPS to Kupffer cells decreased 3.6 times in fucoidin treated rats compared to control rats. Binding of I-125-LPS to endothelial cells decreased 3.5 times in fucoidin treated rats, whereas binding of I-125-LPS to parenchymal cells increased 1.3 times. Binding of I-125-LPS to isolated endothelial and Kupffer cells could be inhibited by polyI for approximately 78% and 75%, respectively, but not by polyA. AcLDL or oxLDL could not inhibit the binding to endothelial or Kupffer cells. LPS itself was able to inhibit the binding of I-125-acLDL and I-125-oxLDL to endothelial cells for 55% and 61%, respectively, and to Kupffer cells for 40% and 65%, respectively. Our results indicate that a scavenger-like receptor on liver endothelial and Kupffer cells is responsible for the binding of LPS, but the binding characteristics of this receptor are different from the binding characteristics of the 220kD scavenger receptor on endothelial and Kupffer cells and the 95kD scavenger receptor on Kupffer cells.