Non-Mannose-Capped Lipoarabinomannan Stimulates Human Peripheral Monocytes to Expression of the “Early Immediate Genes” Tissue Factor and Tumor Necrosis Factor-α

• Published in: Thrombosis research 2001-05, Vol.102 (3), p.273-283
• Main Authors: Møller, Anne-Sophie W., Haug, Kari Bente F., Øvstebø, Reidun, Joø, Gun Britt, Westvik, Åse-Brit, Kierulf, Peter
• Format: Article
• Language: English
• Subjects: Antigens, Bacterial - pharmacology; AraLAM; Biological and medical sciences; Cell physiology; Escherichia coli - chemistry; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Genes, Immediate-Early - drug effects; Humans; Lipopolysaccharides - pharmacology; LPS; Molecular and cellular biology; Monocytes; Monocytes - drug effects; Monocytes - metabolism; Mycobacterium - chemistry; NF-kappa B - drug effects; NF-κ B/c-Rel; Procoagulant activity (TF); Responses to growth factors, tumor promotors, other factors; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Thromboplastin - drug effects; Thromboplastin - genetics; Thromboplastin - metabolism; TNF-α; 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
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(01)00248-1

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-α (TNF-α). 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-κB/Rel and increasing the binding activity of AP-1.