MONOCYTES UP-REGULATE 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 d uring inflammatory response, thrombosis, and development of atheroscle rotic lesions. Such interactions result in modulation of several biolo gical functions of the two cell types. Because both cells, on appropri ate stimulation, synthesize tissue factor (TF), we examined the effect of human umbilical vein endothelial cell (HUVEC)/monocyte coculture o n the expression of TF. We found that the coincubation resulted in TF generation, which was maximal at 4 hours, increased with increasing nu mbers of monocytes, and required mRNA and protein synthesis. Supernata nt from HUVEC/monocyte coculture induced TF activity in HUVECs, but no t in monocytes, indicating that HUVEC were the cells responsible for t he activity, and that soluble mediators were involved. Interleukin-1 b eta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), well-know n inducers of TF in HUVECs, were found in the supernatant from the coc ulture, and specific antibodies directed against either cytokine inhib ited TF generation. The need of IL-1 beta and TNF-alpha synthesis in o rder to elicit TF expression was also suggested by the delay observed in TF mRNA formation and TF activity generation when monocytes were in cubated with HUVECs. IL-1 beta and TNF-alpha antigen levels in the coc ulture supernatant, and, consequently, HUVEC TF expression, were inhib ited in the presence of anti-CD18 monoclonal antibody. These findings emphasize the role of cell-cell contact and cross-talk in the procoagu lant activity, which could be responsible for the thromboembolic compl ications observed in those vascular disorders in which monocyte infilt ration is a common feature. (C) 1997 by The American Society of Hemato logy.