Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 37, Pages 13519-13524Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0403608101
Keywords
P-selectin glycoprotein ligand 1; adhesion; inflammation; hydrodynamic flow
Categories
Funding
- NCRR NIH HHS [P20 RR018758, RR 018758] Funding Source: Medline
- NHLBI NIH HHS [R37 HL034363, R01 HL034363, HL 34363] Funding Source: Medline
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Leukocytes rolling on selectins extrude thin membrane tethers that might stabilize rolling velocities despite marked alterations in wall shear stress. To test this hypothesis, we used differential interference contrast videomicroscopy to visualize formation and breakage of membrane tethers as neurtrophils rolled on P-selectin under flow. Neutrophils rapidly increased tether number as wall shear stress rose and decreased tether number as wall shear stress declined. Membrane tethers invariably accompanied slower, more uniform rolling steps that translated into lower mean rolling velocities and variances in velocity. Unexpectedly, neutrophils, but not fixed cells or microspheres bearing selectin ligands, rolled progressively more slowly and uniformly over time. Scanning electron microscopy revealed that neutrophils developed larger, more complex tether structures as they rolled for longer periods. These data provide evidence that neutrophils stabilize selectin-mediated rolling by rapidly adjusting tether number in response to changes in wall shear stress. Gradual remodeling of tether architecture may further reduce rolling velocities, facilitating integrin-dependent deceleration and arrest on inflamed vascular surfaces.
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