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Originally published as MBC in Press, 10.1091/mbc.E02-05-0275 on October 16, 2002
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Vol. 14, Issue 1, 54-66, January 2003

Rapid Up-Regulation of alpha 4 Integrin-mediated Leukocyte Adhesion by Transforming Growth Factor-beta 1

Rubén A. Bartolomé,* Francisco Sanz-Rodríguez,* Mar M. Robledo, Andrés Hidalgo,dagger and Joaquin TeixidóDagger

Department of Immunology, Centro de Investigaciones Biológicas, Madrid, 28006 Spain

The alpha 4 integrins (alpha 4beta 1 and alpha 4beta 7) are cell surface heterodimers expressed mostly on leukocytes that mediate cell-cell and cell-extracellular matrix adhesion. A characteristic feature of alpha 4 integrins is that their adhesive activity can be subjected to rapid modulation during the process of cell migration. Herein, we show that transforming growth factor-beta 1 (TGF-beta 1) rapidly (0.5-5 min) and transiently up-regulated alpha 4 integrin-dependent adhesion of different human leukocyte cell lines and human peripheral blood lymphocytes (PBLs) to their ligands vascular cell adhesion molecule-1 (VCAM-1) and connecting segment-1/fibronectin. In addition, TGF-beta 1 enhanced the alpha 4 integrin-mediated adhesion of PBLs to tumor necrosis factor-alpha -treated human umbilical vein endothelial cells, indicating the stimulation of alpha 4beta 1/VCAM-1 interaction. Although TGF-beta 1 rapidly activated the small GTPase RhoA and the p38 mitogen-activated protein kinase, enhanced adhesion did not require activation of both signaling molecules. Instead, polymerization of actin cytoskeleton triggered by TGF-beta 1 was necessary for alpha 4 integrin-dependent up-regulated adhesion, and elevation of intracellular cAMP opposed this up-regulation. Moreover, TGF-beta 1 further increased cell adhesion mediated by alpha 4 integrins in response to the chemokine stromal cell-derived factor-1alpha . These data suggest that TGF-beta 1 can potentially contribute to cell migration by dynamically regulating cell adhesion mediated by alpha 4 integrins.


* These authors equally contributed to this work.

dagger Present address: Department of Hematology, Mount Sinai School of Medicine, One Gustave Lane, Levy Place, New York, NY 10029.

Dagger Corresponding author. E-mail address: joaquint{at}cib.csic.es.


Molecular Biology of the Cell
Vol. 14, 54-66, January 2003
Copyright © 2003 by The American Society for Cell Biology



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