Faculty Collaboration Database

Induction of tissue factor on monocytes by adhesion to endothelial cells. J Immunol 1995 May 01;154(9):4768-77

Date

05/01/1995

Pubmed ID

7536780

Scopus ID

2-s2.0-0029008242 (requires institutional sign-in at Scopus site)   91 Citations

Abstract

Activated monocytes express tissue factor (TF), a protein that is important in the pathogenesis of thrombotic disorders. We sought to characterize an adhesion-dependent pathway for monocyte activation. In this study, we showed that adhesion of monocytes to cytokine-activated endothelial cells (EC) increased (approximately 5- to 10-fold) monocyte procoagulant activity (PCA). The PCA was attributed to TF because it was dependent on the coagulation factors VII and X, but not VIII, and was completely blocked by an anti-TF mAb. Direct cell-cell contact between monocytes and EC was required. The induction of TF was rapid, peaked at 30 min, and persisted for 4 h. Northern analysis revealed a rapid (approximately 30 min) increase in TF mRNA following adhesion, distinct from that induced by LPS (approximately 2-4 h). Four-hour TNF-treated EC supported TF expression, but 0.5- and 24-h TNF-treated EC had no effect. An 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 sialyl-Le(x) (sLex) oligosaccharide had no effect. Cross-linking Le(x) on monocytes, but not sLex, significantly increased (approximately 10-fold) the TF expression. Le(x) cross-linking induced TF in 30 min and lasted for 4 h. All seventeen anti-Le(x) mAbs induced significant amount of TF generation, and epitope mapping revealed a single binding epitope on Le(x). These findings indicate that adhesion of monocytes to activated EC induces TF generation, and also suggest that Le(x) may represent an important signaling molecule on monocytes.

Author List

Lo SK, Cheung A, Zheng Q, Silverstein RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blood Coagulation
Blotting, Northern
Cell Adhesion
Cell Adhesion Molecules
Cells, Cultured
E-Selectin
Endothelium, Vascular
Humans
Lewis X Antigen
Monocytes
Signal Transduction
Thromboplastin
Tumor Necrosis Factor-alpha
Umbilical Veins