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

In the present study, we have shown that stimulation of cryopreserved, huma n peripheral blood monocytes with the cell wall components from Gram-negati ve 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 facto r-alpha (TNF-alpha). This was demonstrated both at the protein and the mRNA levels. Antibodies against the CD14 receptor could block the stimulating e ffects. AraLAM was a significantly weaker inducer than LPS, and we speculat e 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, b oth LPS and AraLAM activated the "early immediate genes" through translocat ion of the transcription factor proteins NF-kappaB/Rel and increasing the b inding activity of AP-1. (C) 2001 Elsevier Science Ltd. All rights reserved .