Non-mannose-capped lipoarabinomannan stimulates human peripheral monocytes to expression of the "early immediate genes" tissue factor and tumor necrosis factor-alpha

Thromb Res. 2001 May 1;102(3):273-83. doi: 10.1016/s0049-3848(01)00248-1.

Abstract

In the present study, we have shown that stimulation of cryopreserved, human peripheral blood monocytes with the cell wall components from Gram-negative bacteria, lipopolysaccharide (LPS), and from rapid-growing Mycobacterium sp., non-mannose-capped lipoarabinomannan (AraLAM), both induce expression of the "early immediate genes" tissue factor (TF) and tumor necrosis factor-alpha (TNF-alpha). This was demonstrated both at the protein and the mRNA levels. Antibodies against the CD14 receptor could block the stimulating effects. AraLAM was a significantly weaker inducer than LPS, and we speculate that this may reside in the number of the fatty acids in the part of the molecule that interacts with the CD14/Toll-like receptors (TLR). Finally, both LPS and AraLAM activated the "early immediate genes" through translocation of the transcription factor proteins NF-kappaB/Rel and increasing the binding activity of AP-1.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / pharmacology
  • Escherichia coli / chemistry
  • Gene Expression Regulation / drug effects
  • Genes, Immediate-Early* / drug effects*
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Mycobacterium / chemistry
  • NF-kappa B / drug effects
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Thromboplastin / drug effects
  • Thromboplastin / genetics*
  • Thromboplastin / metabolism
  • Transcription Factor AP-1 / drug effects
  • Transcription Factors / drug effects
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Bacterial
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor AP-1
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • lipoarabinomannan
  • Thromboplastin