Clustering the adhesion molecules VLA-4 (CD49d/CD29) in Jurkat T cells or VCAM-1 (CD106) in endothelial (ECV 304) cells activates the phosphoinositide pathway and triggers Ca2+ mobilization.
Ligation of very late antigen (VLA)-4 (alpha 4 beta 1 integrin) with a cross-linked anti-alpha 4 subunit monoclonal antibody (mAb) triggered a biphasic Ca2+ response in Jurkat cell populations and in peripheral human lymphocytes. Cross-linking vascular cell adhesion molecule (VCAM)-1 (the counter-receptor of VLA-4) in ECV 304 endothelial cells generated a biphasic Ca2+ response. Tumor necrosis factor-alpha-primed human umbilical cord vascular endothelial cells also responded to the cross-linked mAb with a biphasic Ca2+ profile. Ligated VLA-4 (Jurkat cells) or VCAM-1 (ECV 304) stimulated the production of myo-inositol 1,4,5-trisphosphate. ECV 304 cells induced a biphasic Ca2+ response in Fura2-loaded Jurkat cells, whereas a transient response was observed when Jurkat cells were added to Fura2-loaded ECV 304 cells. The Ca2+ responses in these experiments involved VLA-4/VCAM-1 interactions since they were significantly reduced (approximately 80%) by prior treatment of the target cells with the relevant noncross-linked mAb. Close contact between the cells triggered mutual Ca2+ signaling as shown by spectrofluorimetric and confocal microscopy time-dependent recordings. Fibronectin and its CS-1 fragment (V25) triggered a sustained Ca2+ response in Jurkat cells (confocal microscopy). Our results suggest that the VLA-4 and VCAM-1 adhesion molecules can transduce a signal that involves activation of the phosphoinositide pathway and the mobilization of Ca2+.
Ricard
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Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Canada.
Payet
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MD
Dupuis
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D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000096:biosynthesis / Q000378:metabolism*; D016023:Integrins / Q000096:biosynthesis / Q000378:metabolism*; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D010716:Phosphatidylinositols / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013050:Spectrometry, Fluorescence; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism*
D005353:Fibronectins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D010716:Phosphatidylinositols; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium