Non-mannose-capped lipoarabinomannan stimulates human peripheral monocytes to expression of the "early immediate genes" tissue factor and tumor necrosis factor-alpha.
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.
Møller
A W
AW
The R&D Group, Department of Clinical Chemistry, Ullevaal University Hospital, N-0407, Oslo, Norway. a.s.w.moller@ioks.uio.no
Haug
K B
KB
Øvstebø
R
R
Joø
G B
GB
Westvik
A B
AB
Kierulf
P
P
D000942:Antigens, Bacterial / Q000494:pharmacology; D004926:Escherichia coli / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009161:Mycobacterium / Q000737:chemistry; D016328:NF-kappa B / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013925:Thromboplastin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D000942:Antigens, Bacterial; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C050016:lipoarabinomannan; D013925:Thromboplastin