Dynamic alterations of membrane tethers stabilize leukocyte rolling on P-selectin

AUTOR(ES)

Ramachandran, Vishwanath

FONTE

National Academy of Sciences

RESUMO

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 neutrophils 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.

Documentos Relacionados

• P-selectin mediates neutrophil rolling on histamine-stimulated endothelial cells.
• Two by two: The pairings of P-selectin and P-selectin glycoprotein ligand 1
• Role of H1 receptors and P-selectin in histamine-induced leukocyte rolling and adhesion in postcapillary venules.
• Lipoxin A4 stable analogs inhibit leukocyte rolling and adherence in the rat mesenteric microvasculature: Role of P-selectin
• P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation