Lymphocyte Migration Through Monolayers of Endothelial Cell Lines Involves VCAM-1 Signaling Via Endothelial Cell NADPH Oxidase
| Autor: | Heather E. Matheny, Tracy L. Deem, Joan M. Cook-Mills |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Endothelium Immunology Vascular Cell Adhesion Molecule-1 Catalysis Cell Line Mice chemistry.chemical_compound Cell Movement Cell Adhesion medicine Animals Humans Immunology and Allergy Lymphocytes VCAM-1 Lymphocyte homing receptor S1PR1 Mice Inbred BALB C NADPH oxidase biology Immune Sera NADPH Oxidases Actins Microspheres Cell biology Endothelial stem cell Vascular endothelial growth factor A Cross-Linking Reagents medicine.anatomical_structure chemistry Apocynin biology.protein Endothelium Vascular Endothelium Lymphatic Reactive Oxygen Species Signal Transduction |
| Zdroj: | The Journal of Immunology. 164:6550-6559 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.164.12.6550 |
| Popis: | Lymphocytes migrate from the blood across endothelial cells to reach foreign substances sequestered in peripheral lymphoid organs and inflammatory sites. To study intracellular signaling in endothelial cells during lymphocyte migration, we used murine endothelial cell lines that promote lymphocyte migration and constitutively express VCAM-1. The maximum rate of resting splenic lymphocyte migration across monolayers of the endothelial cells occurred at 0–24 h. This migration was inhibited by anti-VCAM-1 or anti-α4 integrin, suggesting that VCAM-1 adhesion was required for migration. To determine whether signals within the endothelial cells were required for migration, irreversible inhibitors of signal transduction molecules were used to pretreat the endothelial cell lines. Inhibitors of NADPH oxidase activity (diphenyleneiodonium and apocynin) blocked migration >65% without affecting adhesion. Because NADPH oxidase catalyzes the production of reactive oxygen species (ROS), we examined whether ROS were required for migration. Scavengers of ROS inhibited migration without affecting adhesion. Furthermore, VCAM-1 ligand binding stimulated NADPH oxidase-dependent production of ROS by the endothelial cells lines and primary endothelial cell cultures. Finally, VCAM-1 ligand binding induced an apocynin-inhibitable actin restructuring in the endothelial cell lines at the location of the lymphocyte or anti-VCAM-1-coated bead, suggesting that an NADPH oxidase-dependent endothelial cell shape change was required for lymphocyte migration. In summary, VCAM-1 signaled the activation of endothelial cell NADPH oxidase, which was required for lymphocyte migration. This suggests that endothelial cells are not only a scaffold for lymphocyte adhesion, but play an active role in promoting lymphocyte migration. |
| Databáze: | OpenAIRE |
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