Mannose receptor-mediated regulation of serum glycoprotein homeostasis

Science. 2002 Mar 8;295(5561):1898-901. doi: 10.1126/science.1069540.

Abstract

Carbohydrates are thought to function as tags that mark circulatory glycoproteins for rapid clearance. To examine the role of the mannose receptor (MR) in glycoprotein clearance, we generated mice genetically deficient in MR. MR-/- mice were defective in clearing proteins bearing accessible mannose and N-acetylglucosamine residues and had elevated levels of eight different lysosomal hydrolases. Proteomic analysis of MR-/- and control mouse sera showed that an additional 4 out of 52 proteins identified were elevated in MR-/- serum. Each of these is up-regulated during inflammation and wound healing. Thus, MR appears to operate as an essential regulator of serum glycoprotein homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Proteins / metabolism*
  • Electrophoresis, Gel, Two-Dimensional
  • Glucuronidase / blood
  • Glucuronidase / metabolism
  • Glycoproteins / blood*
  • Glycoproteins / chemistry
  • Half-Life
  • Homeostasis*
  • Hydrolases / blood
  • Hydrolases / metabolism
  • Inflammation / metabolism
  • Lectins, C-Type*
  • Liver / metabolism
  • Lysosomes / enzymology
  • Mannose / analysis
  • Mannose / metabolism
  • Mannose Receptor
  • Mannose-Binding Lectins*
  • Mass Spectrometry
  • Mice
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Spleen / metabolism
  • Up-Regulation

Substances

  • Blood Proteins
  • Glycoproteins
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Hydrolases
  • Glucuronidase
  • Mannose