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Enhancement of L-Selectin, but Not P-Selectin, Bond Formation Frequency by Convective Flow

Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908

Correspondence: Address reprint requests to William H. Guilford, Dept. of Biomedical Engineering, PO Box 800759, MR5, 1111 415 Lane Road, University of Virginia, Charlottesville, VA 22908. Tel.: 434-924-9908; Fax: 434-982-3870; E-mail: whg2n{at}virginia.edu.

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 noninteracting 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 dyn/cm² to 0.014 ± 0.003 bonds/µm at 1.0 dyn/cm². In contrast, L-selectin tether bond formation increased from 0.017 ± 0.005 bonds/µm at 0.2 dyn/cm² to 0.031 ± 0.005 bonds/µm at 1.0 dyn/cm². L-selectin tether bond formation rates appeared to be enhanced by convective transport, whereas 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. 2005. Biophys. J. 89:1446-1454). 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, to our knowledge, comparing L-selectin and P-selectin bond formation frequencies in shear flow.