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

This report examines the adhesive interactions of human CD4(+) T lymph ocytes with tumor necrosis factor a-activated human endothelial cell m onolayers in an in vitro model that mimics microcirculatory flow condi tions. Resting CD4(+) T cell interactions with activated endothelium c onsisted 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, wh ereas beta(1)-integrins (alpha(4) beta(1)), interacting with endotheli al-expressed vascular cell adhesion molecule 1, participated in rollin g and mediated stable arrest. In contrast, beta(2)-integrins were prim arily involved in spreading and transmigration. These findings highlig ht 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.