Chemokines stimulate human T lymphocyte transendothelial migration to utilize VLA‐4 in addition to LFA‐1

Lymphocyte infiltration in inflammation is induced by the dual actions of chemokines and cell adhesion molecules. The role of LFA‐1 and VLA‐4 in chemokine‐induced T cell transendothelial migration (TEM) across cytokine‐activated endothelium has not been examined. LFA‐1, but not VLA‐4, mediated blood T cell TEM to RANTES, macrophage inflammatory protein‐1α (MIP‐1α), and stromal cell‐derived factor‐1 (SDF‐1), and across tumor necrosis factor α (TNF‐α) or interferon‐γ (IFN‐γ) ‐stimulated endothelial cells (EC). Chemokine stimulation in combination with TNF‐α activation of EC induced TEM, which was partially mediated by VLA‐4. SDF‐1 increased a β1‐integrin activation epitope on T cells and enhanced VLA‐4‐mediated adhesion. Thus, LFA‐1 mediates TEM under most conditions, but VLA‐4 can also mediate TEM, although, in contrast to LFA‐1, this requires exogenous chemokines and EC activation. In addition, an LFA‐1‐ and VLA‐4‐independent pathway of lymphocyte TEM can also be induced by SDF‐1.