Monocytes Upregulate Endothelial Cell Expression of Tissue Factor: A Role for Cell-Cell Contact and Cross-Talk

Monocytes and endothelial cells interact at sites of vascular injury during inflammatory response, thrombosis, and development of atherosclerotic lesions. Such interactions result in modulation of several biological functions of the two cell types. Because both cells, on appropriate stimulation, synthesize tissue factor (TF), we examined the effect of human umbilical vein endothelial cell (HUVEC)/monocyte coculture on the expression of TF. We found that the coincubation resulted in TF generation, which was maximal at 4 hours, increased with increasing numbers of monocytes, and required mRNA and protein synthesis. Supernatant from HUVEC/monocyte coculture induced TF activity in HUVECs, but not in monocytes, indicating that HUVEC were the cells responsible for the activity, and that soluble mediators were involved. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), well-known inducers of TF in HUVECs, were found in the supernatant from the coculture, and specific antibodies directed against either cytokine inhibited TF generation. The need of IL-1 beta and TNF-alpha synthesis in order to elicit TF expression was also suggested by the delay observed in TF mRNA formation and TF activity generation when monocytes were incubated with HUVECs. IL-1 beta and TNF-alpha antigen levels in the coculture supernatant, and, consequently, HUVEC TF expression, were inhibited in the presence of anti-CD18 monoclonal antibody. These findings emphasize the role of cell-cell contact and cross-talk in the procoagulant activity, which could be responsible for the thromboembolic complications observed in those vascular disorders in which monocyte infiltration is a common feature.