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* Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908; and Leukocyte adhesion through L-selectin to
peripheral node addressin (PNAd, also known as
MECA-79 antigen), an L-selectin ligand expressed on
high endothelial venules, has been shown to require a
minimum level of fluid shear stress to sustain rolling interactions (Finger, E.B., K.D. Puri, R. Alon, M.B.
Lawrence, V.H. von Andrian, and T.A. Springer. 1996. Nature (Lond.). 379:266-269). Here, we show that fluid
shear above a threshold of 0.5 dyn/cm2 wall shear stress
significantly enhances HL-60 myelocyte rolling on P-
and E-selectin at site densities of 200/µm2 and below. In
addition, gravitational force is sufficient to detach HL60 cells from P- and E-selectin substrates in the absence, but not in the presence, of flow. It appears that
fluid shear-induced torque is critical for the maintenance of leukocyte rolling. K562 cells transfected with
P-selectin glycoprotein ligand-1, a ligand for P-selectin,
showed a similar reduction in rolling on P-selectin as
the wall shear stress was lowered below 0.5 dyn/cm2.
Similarly, 300.19 cells transfected with L-selectin failed
to roll on PNAd below this level of wall shear stress, indicating that the requirement for minimum levels of
shear force is not cell type specific. Rolling of leukocytes mediated by the selectins could be reinitiated
within seconds by increasing the level of wall shear
stress, suggesting that fluid shear did not modulate receptor avidity. Intravital microscopy of cremaster muscle venules indicated that the leukocyte rolling flux
fraction was reduced at blood centerline velocities less
than 1 mm/s in a model in which rolling is mediated by
L- and P-selectin. Similar observations were made in
L-selectin-deficient mice in which leukocyte rolling is
entirely P-selectin dependent. Leukocyte adhesion
through all three selectins appears to be significantly
enhanced by a threshold level of fluid shear stress.
Department of
Microbiology and Immunology, Northwestern Medical School, Chicago, Illinois 60611
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