title: Ligation of L-selectin on T lymphocytes activates beta1 integrins and promotes adhesion to fibronectin.
abstract: Lymphocyte recirculation is dependent on families of adhesion molecules expressed on lymphocytes and their sequential interaction with ligands expressed on high endothelial venules in secondary lymphoid organs such as peripheral lymph nodes. By binding its carbohydrate-based ligands, L-selectin initiates this cascade of molecular interactions, supporting the rolling of lymphocytes along high endothelial venules. Subsequent activation of lymphocyte integrins leads to cell arrest followed by lymphocyte extravasation. Here, we demonstrate stimulated adhesion of PBL and Jurkat T cells to immobilized fibronectin following treatment with (1) GlyCAM-1, a physiologic ligand for L-selectin, and (2) cross-linked anti-L-selectin mAbs. We also utilize a solution binding assay to detect early changes in integrin activity, including affinity modulation and/or integrin clustering, and distinguish these from later postreceptor binding events such as changes in cell shape and spreading. With the Jurkat cell line, GlyCAM-1 and fucoidin (an L-selectin ligand mimetic) induce the binding of soluble fibronectin. In contrast, stimulation through the Jurkat TCR fails to promote binding to soluble ligand even though TCR cross-linking markedly enhances adhesion to immobilized fibronectin. These data suggest that L-selectin and the TCR promote adhesion through distinct mechanisms. Finally, we demonstrate that beta1 integrins are preferentially activated on naive T cells through the L-selectin pathway. Together with our previous studies showing similar activation of beta2 integrins on the naive T cell subset, these data suggest that signals delivered though L-selectin participate in the preferential recruitment of these cells to peripheral lymph nodes.
authors.affiliation: Department of Anatomy, Program in Immunology, University of California, San Francisco 94143, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Giblin
authors.forename: S T
authors.initials: ST
authors.lastname: Hwang
authors.forename: T R
authors.initials: TR
authors.lastname: Katsumoto
authors.forename: S D
authors.initials: SD
authors.lastname: Rosen
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D019012:Integrin beta1 / Q000378:metabolism* / Q000502:physiology; D007399:Interphase / Q000187:drug effects / Q000276:immunology; D019169:Jurkat Cells; D019041:L-Selectin / Q000276:immunology* / Q000378:metabolism*; D008954:Models, Biological; D009077:Mucins / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D009077:Mucins; D011134:Polysaccharides; D011948:Receptors, Antigen, T-Cell; D019041:L-Selectin; C075185:sulfated glycoprotein p50; C007789:fucoidan