Signaling Pathways of Tissue Factor Expression in Monocytes and Macrophages.

The expression of surface tissue factor by cells of the monocyte/macrophage lineage is a major contributor to the development and progression of local and systemic inflammatory reactions. A wide variety of extracellular stimuli act to upregulate tissue factor (TF), the principal inducer of the coagulation cascade in vivo. Since both the coagulation cascade and TF have multiple roles, the expression of TF has consequences both for the inflammatory milieu and for the monocyte. TF expression is controlled primarily at the transcriptional level, particularly by activation of AP-1 and NF-κB transcription factors. Control is mediated both at the level of NF-κB and AP-1 nuclear translocation and DNA binding and by altering their transactivation potential; however, recent data suggests that while these factors are necessary, they are not sufficient for TF expression. Similarly, a number of intracellular signaling cascades have been studied and may affect TF upregulation both at the transcriptional and post-transcriptional level. In particular, the roles of protein tyrosine kinases, protein kinase C and the downstream Mitogen Activated Protein Kinases (MAPK) suggest that signal integration occurs at many stages. In this review, the roles of monocyte TF are briefly overviewed and the signaling pathways regulating TF gene expression and functional activity are examined in detail. [ABSTRACT FROM AUTHOR]