Ligation of L-Selectin on T Lymphocytes Activates β1 Integrins and Promotes Adhesion to Fibronectin

Patricia A. Giblin, Samuel T Hwang, Tamiko R. Katsumoto, Steven D. Rosen

Research output: Contribution to journalArticle

87 Scopus citations

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 β1 integrins are preferentially activated on naive T cells through the L-selectin pathway. Together with our previous studies showing similar activation of β2 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.

Original languageEnglish (US)
Pages (from-to)3498-3507
Number of pages10
JournalJournal of Immunology
Volume159
Issue number7
StatePublished - Oct 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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