Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions
| Autor: | Stephen Shaw, G A van Seventer, L D Beall, Norma Graber, Walter Newman, Yoji Shimizu, Kevin J. Horgan, T V Gopal |
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| Rok vydání: | 1991 |
| Předmět: |
Naive T cell
T-Lymphocytes T cell Vascular Cell Adhesion Molecule-1 Biology Ligands Transfection Mice L Cells Antigens CD T-Lymphocyte Subsets Cell Adhesion medicine Animals Humans Cytotoxic T cell Lymphocyte function-associated antigen 1 Cell adhesion Cells Cultured Cell adhesion molecule ZAP70 Articles Cell Biology Intercellular Adhesion Molecule-1 Lymphocyte Function-Associated Antigen-1 Cell biology medicine.anatomical_structure CD4 Antigens embryonic structures cardiovascular system Neural cell adhesion molecule Endothelium Vascular E-Selectin Cell Adhesion Molecules |
| Zdroj: | Scopus-Elsevier The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.113.5.1203 |
| Popis: | T cell adhesion to endothelium is critical to lymphocyte recirculation and influx into sites of inflammation. We have systematically analyzed the role of four receptor/ligand interactions that mediate adhesion of peripheral human CD4+ T cells to cultured human umbilical vein endothelial cells (HUVEC): T cell LFA-1 binding to ICAM-1 and an alternative ligand ("ICAM-X"), T cell VLA-4 binding to VCAM-1, and T cell binding to ELAM-1. Contributions of these four pathways depend on the activation state of both the T cell and HUVEC, and the differentiation state of the T cell. ELAM-1 plays a significant role in mediating adhesion of resting CD4+ T cells to activated HUVEC. LFA-1 adhesion dominates with PMA-activated T cells but the strength and predominant LFA-1 ligand is determined by the activation state of the HUVEC; while ICAM-1 is the dominant ligand on IL-1-induced HUVEC, "ICAM-X" dominates binding to uninduced HUVEC. Adhesion via VLA-4 depends on induction of its ligand VCAM-1 on activated HUVEC; PMA activation of T cells augments VLA-4-mediated adhesion, both in the model of T/HUVEC binding and in a simplified model of T cell adhesion to VCAM-1-transfected L cells. Unlike LFA-1 and VLA-4, ELAM-1-mediated adhesion is not increased by T cell activation. Differential expression of adhesion molecules on CD4+ T cell subsets understood to be naive and memory cells also regulates T/HUVEC adhesion. Naive T cell adhesion to HUVEC is mediated predominantly by LFA-1 with little or no involvement of the VLA-4 and ELAM-1 pathways. In contrast, memory T cells bind better to HUVEC and utilize all four pathways. These studies demonstrate that there are at least four molecular pathways mediating T/HUVEC adhesion and that the dominance/hierarchy of these pathways varies dramatically with the activation state of the interacting cells and the differentiation state of the T cell. |
| Databáze: | OpenAIRE |
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