Critical role of lipopolysaccharide-binding protein and CD14 in immune responses against gram-negative bacteria

J Immunol. 2001 Sep 1;167(5):2759-65. doi: 10.4049/jimmunol.167.5.2759.

Abstract

LPS-binding protein (LBP) and CD14 potentiate cell activation by LPS, contributing to lethal endotoxemia. We analyzed the contribution of LBP/CD14 in models of bacterial infection. Mice pretreated with mAbs neutralizing CD14 or LBP showed a delay in TNF-alpha production and died of overwhelming infection within 24 h, after a challenge with 250 CFU of virulent Klebsiella pneumoniae. Blockade of TNF-alpha also increased lethality, whereas pretreatment with TNF-alpha protected mice, even in the presence of LBP and CD14 blockade. Anti-LBP or anti-CD14 mAbs did not improve or decrease lethality with a higher inoculum (10(5) K. pneumoniae) and did not affect outcome following injections of low or high inocula of Escherichia coli O111. These results point to the essential role of LBP/CD14 in innate immunity against virulent bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins*
  • Animals
  • Antibodies, Monoclonal
  • Bacteremia / etiology
  • Bacteremia / immunology
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism*
  • Endotoxemia / immunology
  • Escherichia coli / immunology
  • Escherichia coli / pathogenicity
  • Female
  • Gram-Negative Bacteria / immunology*
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Negative Bacterial Infections / etiology
  • Gram-Negative Bacterial Infections / immunology
  • Klebsiella pneumoniae / immunology
  • Klebsiella pneumoniae / pathogenicity
  • Lipopolysaccharide Receptors / metabolism*
  • Lipopolysaccharides / metabolism*
  • Lipopolysaccharides / toxicity
  • Membrane Glycoproteins*
  • Mice
  • Neutralization Tests
  • Neutrophils / immunology
  • Sepsis / etiology
  • Sepsis / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / pharmacology
  • Virulence

Substances

  • Acute-Phase Proteins
  • Antibodies, Monoclonal
  • Carrier Proteins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide-binding protein