Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts

Eur J Immunol. 2001 Nov;31(11):3153-64. doi: 10.1002/1521-4141(200111)31:11<3153::aid-immu3153>3.0.co;2-0.

Abstract

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • CD47 Antigen
  • Carrier Proteins / metabolism
  • Ceramides / metabolism*
  • Drosophila Proteins*
  • Humans
  • Inflammation / metabolism
  • Ligands
  • Lipopolysaccharide Receptors / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Macrophage-1 Antigen / metabolism
  • Membrane Glycoproteins / metabolism
  • Membrane Microdomains / metabolism*
  • Membrane Proteins*
  • Monocytes / metabolism*
  • Receptors, Cell Surface / metabolism
  • Tetraspanin 28
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • Antigens, CD
  • CD47 Antigen
  • CD47 protein, human
  • CD81 protein, human
  • Carrier Proteins
  • Ceramides
  • Drosophila Proteins
  • Ligands
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Macrophage-1 Antigen
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Tetraspanin 28
  • Toll-Like Receptor 4
  • Toll-Like Receptors