Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells

Biochem J. 1997 Mar 1;322 ( Pt 2)(Pt 2):567-73. doi: 10.1042/bj3220567.

Abstract

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Physiological aspects of the catabolism of non-enzymically glycated proteins were studied in vivo and in vitro. AGE-modified BSA (AGE-BSA) was a mixture of high-Mr (cross-linked), monomeric and low-Mr (fragmented) AGE-BSA. After intravenous administration in rat, all three fractions of AGE-BSA accumulated extremely rapidly and almost exclusively in liver. Uptake in liver endothelial, Kupffer and parenchymal cells accounted for approx. 60%, 25% and 10-15% respectively of hepatic elimination. Both cross-linked and monomeric AGE-BSA were efficiently taken up and degraded in cultures of purified liver endothelial and Kupffer cells. Endocytosis of AGE-BSA by these cells was inhibited by several ligands for the scavenger receptor. Although 125I-Hb was not endocytosed in vitro, 125I-AGE-Hb was effectively endocytosed by a mechanism that was subject to inhibition by AGE-BSA. Endocytosis of N-terminal propeptide of type I procollagen, a physiological ligand for the scavenger receptor, was effectively inhibited by AGE-Hb and AGE-BSA. We conclude that AGE-modification renders macromolecules susceptible for elimination via the scavenger receptor of both liver endothelial and Kupffer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Endocytosis*
  • Endothelium / cytology
  • Endothelium / metabolism*
  • Glycation End Products, Advanced / pharmacokinetics*
  • Kupffer Cells / cytology
  • Kupffer Cells / metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Membrane Proteins*
  • Metabolic Clearance Rate
  • Rats
  • Receptors, Immunologic / metabolism*
  • Receptors, Lipoprotein*
  • Receptors, Scavenger
  • Scavenger Receptors, Class B

Substances

  • Glycation End Products, Advanced
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, Lipoprotein
  • Receptors, Scavenger
  • Scarb1 protein, mouse
  • Scavenger Receptors, Class B