P-SELECTIN AND VASCULAR CELL-ADHESION MOLECULE-1 MEDIATE ROLLING AND ARREST, RESPECTIVELY, OF CD4(+) T-LYMPHOCYTES ON TUMOR-NECROSIS-FACTOR ALPHA-ACTIVATED VASCULAR ENDOTHELIUM UNDER FLOW

This report examines the adhesive interactions of human CD4(+) T lymphocytes with tumor necrosis factor a-activated human endothelial cell monolayers in an in vitro model that mimics microcirculatory flow conditions. Resting CD4(+) T cell interactions with activated endothelium consisted of initial attachment followed by rolling, stable arrest, and then spreading and transendothelial migration. P-selectin, but not E-, or L-selectin, mediated most of this initial contact and rolling, whereas beta(1)-integrins (alpha(4) beta(1)), interacting with endothelial-expressed vascular cell adhesion molecule 1, participated in rolling and mediated stable arrest. In contrast, beta(2)-integrins were primarily involved in spreading and transmigration. These findings highlight an important role for P-selectin and suggest discrete functions for beta(1)- and beta(2)-integrins during lymphocyte recruitment to sites of immune-mediated inflammation.