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4 Integrin Signaling Activates Phosphatidylinositol 3-Kinase and Stimulates T Cell Adhesion to Intercellular Adhesion Molecule-1 to a Similar Extent As CD3, but Induces a Distinct Rearrangement of the Actin Cytoskeleton1
Toronto General Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Dynamic regulation of 
2 integrin-dependent adhesion
is critical for a wide array of T cell functions. We previously showed
that binding of high-affinity 
41
integrins to VCAM-1 strengthens L2
integrin-mediated adhesion to ICAM-1. In this study, we compared
2 integrin-mediated adhesion of T cells to ICAM-1 under
two different functional contexts: 4 integrin signaling
during emigration from blood into tissues and CD3 signaling during
adhesion to APCs and target cells. Cross-linking either
4 integrin or CD3 on Jurkat T cells induced adhesion to
ICAM-1 of comparable strength. Adhesion was dependent on
phosphatidylinositol (PI) 3-kinase but not p44/42 mitogen-activated
protein kinase (extracellular regulated kinase 1/2), because it was
inhibited by wortmannin and LY294002 but not U0126. These data suggest
that PI 3-kinase is a ubiquitous regulator of 2
integrin-mediated adhesion. A distinct morphological change consisting
of Jurkat cell spreading and extension of filopodia was induced by
4 integrin signaling. In contrast, CD3 induced radial
rings of cortical actin polymerization. Inhibitors of PI 3-kinase and
extracellular regulated kinase 1/2 did not affect 4
integrin-induced rearrangement of the actin cytoskeleton, but treatment
with ionomycin, a Ca2+ ionophore, modulated cell morphology
by reducing filopodia and promoting lamellipodia formation.
Qualitatively similar morphological and adhesive changes to those
observed with Jurkat cells were observed following 4
integrin or CD3 stimulation of human peripheral blood T
cells.
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