We have employed an in vitro model consisting of human umbilical vein endothelial cells (EC) grown on type I collagen to study the role of tissue factor (TF) in the interactions of mononuclear phagocytes (MP) with endothelium during their (1) initial exit from the blood, and (2) subsequent clearance from tissues by basal-to-apical migration across vascular and/or lymphatic endothelium (reverse transmigration). Though not expressed on unstimulated monocytes, TF was induced on MP during coculture with EC or by stimulation with LPS. TF was not observed on EC cultured either in the presence or absence of MP. Adhesion of LPS-stimulated monocytes, but not control monocytes, to unstimulated or TNF-activated EC was inhibited 35 ± 7% (4 experiments) by anti-TF mAb VIC7 but not by anti-factor VII mAb. VIC7 strongly inhibited reverse transmigration, by 77 ± 22% (12 experiments) over 48 hours, but control mAbs did not. Soluble recombinant TF also impeded reverse migration by 53 ± 19% (3 experiments), likely by acting as a competitor for endogenous TF. Eighty-two percent more EC adhered to surfaces containing immobilized TF than to surfaces containing immobilized ovalbumin, and this increase was abrogated by VIC7. However, VIC7 did not act as a general inhibitor of adhesion or motility, as it did not prevent chemotaxis of TF+ MP to fMLP in microporous filters. Together, these data suggest that TF on MP surfaces interacts with an unknown ligand on EC, under conditions possibly relevant to sepsis and to clearance of MP from tissues.
|State||Published - Dec 1 1997|