Low force decelerates L-selectin dissociation from P-selectin glycoprotein ligand-1 and endoglycan

J Biol Chem. 2004 Jan 16;279(3):2291-8. doi: 10.1074/jbc.M310396200. Epub 2003 Oct 22.

Abstract

Selectin-ligand interactions mediate the tethering and rolling of circulating leukocytes on vascular surfaces during inflammation and immune surveillance. To support rolling, these interactions are thought to have rapid off-rates that increase slowly as wall shear stress increases. However, the increase of off-rate with force, an intuitive characteristic named slip bonds, is at odds with a shear threshold requirement for selectin-mediated cell rolling. As shear drops below the threshold, fewer cells roll and those that do roll less stably and with higher velocity. We recently demonstrated a low force regime where the off-rate of P-selectin interacting with P-selectin glycoprotein ligand-1 (PSGL-1) decreased with increasing force. This counter-intuitive characteristic, named catch bonds, might partially explain the shear threshold phenomenon. Because L-selectin-mediated cell rolling exhibits a much more pronounced shear threshold, we used atomic force microscopy and flow chamber experiments to determine off-rates of L-selectin interacting with their physiological ligands and with an antibody. Catch bonds were observed at low forces for L-selectin-PSGL-1 interactions coinciding with the shear threshold range, whereas slip bonds were observed at higher forces. These catch-slip transitional bonds were also observed for L-selectin interacting with endoglycan, a newly identified PSGL-1-like ligand. By contrast, only slip bonds were observed for L-selectin-antibody interactions. These findings suggest that catch bonds contribute to the shear threshold for rolling and are a common characteristic of selectin-ligand interactions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Humans
  • L-Selectin / chemistry*
  • L-Selectin / metabolism
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Microscopy, Atomic Force
  • Mucins / chemistry*
  • Mucins / metabolism

Substances

  • Membrane Glycoproteins
  • Mucins
  • P-selectin ligand protein
  • endoglycan
  • L-Selectin