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Monocytes upregulate endothelial cell expression of tissue factor: a role
for cell-cell contact and cross-talk
E Napoleone, A Di Santo and R Lorenzet
Antonio Taticchi Unit for Atherosclerosis and Thrombosis, Department of
Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche
Mario Negri Sud, Santa Maria Imbaro, Italy.
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.
Volume 89,
Issue 2,
pp. 541-549,
01/15/1997
Copyright © 1997 by The American Society of Hematology
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