Cutting edge: cell surface expression and lipopolysaccharide signaling via the toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages

J Immunol. 2000 Apr 1;164(7):3471-5. doi: 10.4049/jimmunol.164.7.3471.

Abstract

The human MD-2 molecule is associated with the extracellular domain of human Toll-like receptor 4 (TLR4) and greatly enhances its LPS signaling. The human TLR4-MD-2 complex thus signals the presence of LPS. Little is known, however, about cell surface expression and LPS signaling of the TLR4-MD-2 complex in vivo. We cloned mouse MD-2 molecularly and established a unique mAb MTS510, which reacted selectively with mouse TLR4-MD-2 but not with TLR4 alone in flow cytometry. Mouse MD-2 expression in TLR4-expressing cells enhanced LPS-induced NF-kappaB activation, which was clearly inhibited by MTS510. Thioglycolate-elicited peritoneal macrophages expressed TLR4-MD-2, which was rapidly down-regulated in the presence of LPS. Moreover, LPS-induced TNF-alpha production by peritoneal macrophages was inhibited by MTS510. Collectively, the TLR4-MD-2 complex is expressed on macrophages in vivo and senses and signals the presence of LPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / physiology
  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / biosynthesis
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism
  • Antigens, Surface / physiology*
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Drosophila Proteins*
  • Lipopolysaccharides / immunology*
  • Lymphocyte Antigen 96
  • Macrophage Activation
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology*
  • Signal Transduction / immunology*
  • Thioglycolates / pharmacology
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Transfection

Substances

  • Adjuvants, Immunologic
  • Antigens, Surface
  • Drosophila Proteins
  • Lipopolysaccharides
  • Lymphocyte Antigen 96
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Thioglycolates
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Associated data

  • GENBANK/AB018550