The integrin VLA-4 supports tethering and rolling in flow on VCAM-1.
Selectins have previously been shown to tether a flowing leukocyte to a vessel wall and mediate rolling. Here, we report that an intergrin, VLA-4, can also support tethering and rolling. Blood T lymphocytes and alpha 4 integrin-transfected cells can tether in shear flow, and then roll, through binding of the intergrin VLA-4 to purified VCAM-1 on the wall of a flow chamber. VLA-4 transfectants showed similar tethering and rolling on TNF-stimulated endothelium. Tethering efficiency, rolling velocity, and resistance to detachment are related to VCAM-1 density. Tethering and rolling did not occur on ICAM-1, fibronectin, or fibronectin fragments, and tethering did not require integrin activation or the presence of an alpha 4 cytoplasmic domain. Arrest of rolling cells on VCAM-1 occurred spontaneously, and/or was triggered by integrin activating agents Mn2+, phorbol ester, and mAb TS2/16. These agents, and the alpha 4 cytoplasmic domain, promoted increased resistance to detachment. Together the results show that VLA-4 is a versatile integrin that can mediate tethering, rolling, and firm arrest on VCAM-1.
Alon
R
R
Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115.
Kassner
P D
PD
Carr
M W
MW
Finger
E B
EB
Hemler
M E
ME
Springer
T A
TA
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D016029:Receptors, Very Late Antigen / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1