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-1alpha (MIP-1alpha), and stromal cell-derived factor-1 (SDF-1), and across tumor necrosis factor alpha (TNF-alpha) or interferon-gamma (IFN-gamma) -stimulated endothelial cells (EC). Chemokine stimulation in combination with TNF-alpha activation of EC induced TEM, which was partially mediated by VLA-4. SDF-1 increased a beta1-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.