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.
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
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Issekutz
D002465:Cell Movement / Q000276:immunology / Q000502:physiology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000494:pharmacology / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C515255:CXCL12 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D019402:Macrophage Inflammatory Proteins; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma