Enhancement of L-selectin, but not P-selectin, Bond Formation Frequency by Convective Flow
Christopher Dwight Paschall 1, William H. Guilford 1* and Michael B. Lawrence 1
1 University of Virginia
* To whom correspondence should be addressed. E-mail: guilford{at}virginia.edu.
Submitted on October 5, 2006
Revised on November 19, 2006
Accepted on 27 August 2007
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Abstract |
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L-selectin mediated leukocyte rolling has been proposed to require a high rate of bond formation compared to that of P-selectin to compensate for its much higher off-rate. To test this hypothesis, a microbead system was utilized to measure relative L-selectin and P-selectin bond formation rates on their common ligand P-selectin Glycoprotein Ligand-1 (PSGL-1) under shear flow. Using video microscopy, we tracked selectin-coated microbeads to detect the formation frequency of adhesive tether bonds. From velocity distributions of non-interacting and interacting microbeads we observed that tether bond formation rates for P-selectin on PSGL-1 decreased with increasing wall shear stress, from 0.14 ± 0.04 bonds/µm at 0.2 dyne/cm2 to 0.014 ± 0.003 bonds/µm at 1.0 dyne/cm2. In contrast, L-selectin tether bond formation increased from 0.017 ± 0.005 bonds/µm at 0.2 dyne/cm2 to 0.031 ± 0.005 bonds/µm at 1.0 dyne/cm2. L-selectin tether bond formation rates appeared to be enhanced by convective transport while P-selectin rates were inhibited. The transition force for the L-selectin catch-slip transition of 44 pN/bond agreed well with theoretical models (Pereverzev et al., Biophys. J., 2005). Despite catch bond behavior, hydrodymanic shear thresholding was not detected with L-selectin beads rolling on PSGL-1. We speculate that shear flow generated compressive forces may enhance L-selectin bond formation relative to that of P-selectin and that L-selectin bonds with PSGL-1 may be tuned for the compressive forces characteristic of leukocyte-leukocyte collisions during secondary capture on the blood vessel wall. This is the first report comparing L-selectin and P-selectin bond formation frequencies in shear flow.
Key Words:
L-selectin, P-selectin, PSGL-1, bond formation, secondary capture
