Essential role of MD-2 in B-cell responses to lipopolysaccharide and Toll-like receptor 4 distribution

J Endotoxin Res. 2002;8(6):449-52. doi: 10.1179/096805102125001055.

Abstract

Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signaling in a variety of cell types. MD-2 is associated with the extracellular domain of TLR4 and augments TLR4-dependent LPS responses in vitro. Moreover, mice lacking MD-2 (MD-2(-/-)) do not respond to LPS, survive endotoxin shock, and are susceptible to Salmonella typhimurium infection. Here, we further show that B cells lacking MD-2 do not up-regulate CD23 in response to LPS. TLR4 predominantly resides in the Golgi apparatus without MD-2. MD-2 is essential for LPS responses in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / pharmacology*
  • B-Lymphocytes / immunology*
  • Cell Culture Techniques
  • Fibroblasts
  • Golgi Apparatus
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / pharmacology*
  • Mice
  • Receptors, Cell Surface / genetics
  • Receptors, IgE / biosynthesis
  • Salmonella Infections, Animal
  • Salmonella typhimurium / pathogenicity
  • Signal Transduction
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Up-Regulation

Substances

  • Antigens, Surface
  • LY96 protein, human
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, IgE
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors