Activated monocytes express tissue factor (TF), a protein that is impo
rtant in the pathogenesis of thrombotic disorders. We sought to charac
terize an adhesion-dependent pathway for monocyte activation. In this
study, we showed that adhesion of monocytes to cytokine-activated endo
thelial cells (EC) increased (similar to 5- to 10-fold) monocyte proco
agulant activity (PCA). The PCA was attributed to TF because it was de
pendent on the coagulation factors VII and X, but not VIII, and was co
mpletely blocked by an anti-TF mAb. Direct cell-cell contact between m
onocytes and EC was required. The induction of TF was rapid, peaked at
30 min, and persisted for 4 h. Northern analysis revealed a rapid (si
milar to 30 min) increase in TF mRNA following adhesion, distinct from
that induced by LPS (similar to 2-4 h). Four-hour TNF-treated EC supp
orted TF expression, but 0.5- and 24-h TNF-treated EC had no effect. A
n anti-E-selectin mAb (H18/7) exerted partial inhibition, whereas anti
-VCAM-1, ICAM-1, and CD11/CD18 mAbs had no inhibition. Synthetic Lewis
X (Le(x)) oligosaccharide partially blocked TF induction, whereas sia
lyl-Le(x) (sLe(x)) oligosaccharide had no effect. Cross-linking Le(x)
on monocytes, but not sLe(x), significantly increased (similar to-10-f
old) the TF expression. Le(x) cross-linking induced TF in 30 min and l
asted for 4 h. All seventeen anti-Le(x) mAbs induced significant amoun
t of TF generation, and epitope mapping revealed a single binding epit
ope on Le(x). These findings indicate that adhesion of monocytes to ac
tivated EC induces TF generation, and also suggest that Le(x) may repr
esent an important signaling molecule on monocytes.