Role of Tissue Factor in Adhesion of Mononuclear Phagocytes to and Trafficking Through Endothelium In Vitro

An in vitro model consisting of endothelium grown oncollagen was used to investigate how mononuclear phagocytes traverse endothelium in the basal-to-apical direction (reverse transmigration), a process that mimics their migration across vascular and/orlymphatic endothelium during atherosclerosis and resolution ofinflammation, respectively. Monoclonal antibody (MoAb) VIC7 againsttissue factor (TF) inhibited reverse transmigration by 77%.Recombinant tissue factor fragments containing at least six amino acidsC-terminal to residue 202 also strongly inhibited reversetransmigration. TF was absent on resting monocytes but was induced onthese cells after initial apical-to-basal transendothelial migration.Two additional observations suggest that TF is involved in adhesion between mononuclear phagocytes and endothelium: (1) when monocytes wereincubated with lipopolysaccharide (LPS) to stimulate expression of TFbefore they were added to endothelium, VIC7 or soluble TF modestlyinhibited their adhesion to the apical endothelial surface, each byabout 35%; and (2) endothelial cells specifically bound to surfacescoated with TF fragments containing amino acids 202-219. This bindingwas blocked by anti-TF MoAb, suggesting that endothelial cells bear areceptor for TF. These data suggest that mononuclear phagocytes use TF, perhaps as an adhesive protein, to exit sites ofinflammation.