Lipopolysaccharide (LPS) Recognition in Macrophages. Participation of LPS-binding Protein and CD14 in LPS-induced Adaptation in Rabbit Peritoneal Exudate Macrophages

J Clin Invest. 1993 Oct;92(4):2053-9. doi: 10.1172/JCI116801.

Abstract

Exposure of rabbit peritoneal exudate macrophages (PEM) or whole blood to picomolar concentrations of LPS induces adaptation or hyporesponsiveness to LPS. Because of the importance of plasma LPS-binding protein (LBP) and the macrophage cell membrane protein CD14 in recognition of LPS, we examined the effect of LBP on LPS-induced adaptation in PEM. PEM exposed to LPS in the presence of LBP for 8 h were markedly less responsive to subsequent stimulation by LPS than monocytes/macrophages (M phi) adapted in the absence of LBP. LPS-induced expression of TNF was sharply reduced in LBP-LPS-adapted PEM, but in contrast these cells remained fully responsive to Staphylococcus aureus peptidoglycan. We considered that specific hyporesponsiveness in LPS-adapted M phi or in blood monocytes could be due to decreased expression of CD14 or diminished binding of LBP-LPS complexes to CD14. However, flow cytometry analysis revealed only minimal reduction of CD14 expression or CD14-dependent binding of a fluorescent LPS derivative when normo- and hyporesponsive cells were compared. These results show that complexes of LPS and LBP are more effective than LPS alone in inducing adaptation to LPS, and LPS-induced hyporesponsiveness probably results from changes in cellular elements distinct from CD14 that are involved in either LPS recognition or LPS-specific signal transduction.

Publication types

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

MeSH terms

  • Acclimatization
  • Acute-Phase Proteins / metabolism
  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Carrier Proteins / metabolism*
  • Cell Survival / drug effects
  • Clone Cells
  • Kinetics
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Membrane Glycoproteins*
  • Rabbits
  • Recombinant Proteins / pharmacology
  • Salmonella
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Acute-Phase Proteins
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Carrier Proteins
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide-binding protein