Distinct kinetic and mechanical properties govern selectin-leukocyte interactions

William D. Hanley, Denis Wirtz, K Konstantopoulos

Research output: Contribution to journalArticle

Abstract

Leukocytes are recruited from the bloodstream to sites of inflammation by the selectin family of adhesion receptors. In vivo and in vitro studies reveal distinctive rolling velocities of polymorphonuclear leukocytes over E-, P- and L-selectin substrates. The kinetic and mechanical properties of the selectin-ligand bonds responsible for these differences at the single-molecule level are not well understood. Using single-molecule force spectroscopy, we probe in situ the rupture force, unstressed off-rate and reactive compliance of single selectin receptors to single ligands on whole human polymorphonuclear leukocytes (PMNs) under conditions that preserve the proper orientation and post-translational modifications of the selectin ligands. Single L-selectin bonds to PMNs were more labile than either E- or P-selectin in the presence of an applied force. This outcome, along with a higher unstressed off-rate and a higher reactive compliance, explain the faster L-selectin-mediated rolling. By quantifying binding frequency in the presence of a specific blocking monoclonal antibody or following enzyme treatment, we determined that P-selectin glycoprotein ligand-1 is a high-affinity ligand for E-selectin on PMNs under force. The rupture force spectra and corresponding unstressed off-rate and reactive compliance of selectin-ligand bonds provide mechanistic insights that might help to explain the variable rolling of leukocytes over different selectin substrates.

Original languageEnglish (US)
Pages (from-to)2503-2511
Number of pages9
JournalJournal of Cell Science
Volume117
Issue number12
DOIs
StatePublished - May 15 2004

Fingerprint

Selectins
Leukocytes
L-Selectin
Ligands
Compliance
P-Selectin
Rupture
Neutrophils
Leukocyte Rolling
Blocking Antibodies
E-Selectin
Post Translational Protein Processing
Monoclonal Antibodies
Inflammation
Enzymes

Keywords

  • Force spectroscopy
  • Leulocyte
  • Offrate
  • PSGL-1
  • Selectine

ASJC Scopus subject areas

  • Cell Biology

Cite this

Distinct kinetic and mechanical properties govern selectin-leukocyte interactions. / Hanley, William D.; Wirtz, Denis; Konstantopoulos, K.

In: Journal of Cell Science, Vol. 117, No. 12, 15.05.2004, p. 2503-2511.

Research output: Contribution to journalArticle

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