Journal
JOURNAL OF CELL BIOLOGY
Volume 166, Issue 6, Pages 913-923Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200403144
Keywords
leukocyte; PSGL-1; inflammation; lymphocyte homing; selectin
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Funding
- NHLBI NIH HHS [HL 65631, R01 HL065631] Funding Source: Medline
- NIAID NIH HHS [AI 44902, R01 AI044902, R21 AI044902] Funding Source: Medline
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Flow-enhanced cell adhesion is an unexplained phenomenon that might result from a transport-dependent increase in on-rates or a force-dependent decrease in off-rates of adhesive bonds. L-selectin requires a threshold shear to support leukocyte rolling on P-selectin glycoprotein ligand-1 (PSGL-1) and other vascular ligands. Low forces decrease L-selectin-PSGL-1 off-rates (catch bonds), whereas higher forces increase off-rates (slip bonds). We determined that a force-dependent decrease in off-rates dictated flow-enhanced rolling of L-selectin-bearing microspheres or neutrophils on PSGL-1. Catch bonds enabled increasing force to convert short-lived tethers into longer-lived tethers, which decreased rolling velocities and increased the regularity of rolling steps as shear rose from the threshold to an optimal value. As shear increased above the optimum, transitions to slip bonds shortened tether lifetimes, which increased rolling velocities and decreased rolling regularity. Thus, force-dependent alterations of bond lifetimes govern L-selectin-dependent cell adhesion below and above the shear optimum. These findings establish the first biological function for catch bonds as a mechanism for flow-enhanced cell adhesion.
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