Adhesion efficiency vs. contact duration elucidates the dynamics of integrin and selectin function

A. D. Tavlor, S. Neelameqham, C. W. Smith, J. D. Heliums, S. I. Simon

Research output: Contribution to journalArticle

Abstract

Leukocytes home to sites of tissue injury by the sequential adhesion of L-selectin and β2-integrin receptors to counter-structures on the vascular endothelium. Recent evidence indicates that selectins mediate cell rolling by forming few bonds with a rapid on and off rate. The transition between se led in tethering and integrin dependent firm adhesion has yet to be elucidated. We are studying homotypic neutrophil aggregation as a model of integrin and select in dependent adhesion. Cone and plate viscometry was employed to expose cell suspensions to a range of shear rates (G =50 s-1 to 2000 s-t) and consequent cell contact durations (At-n/G). Neutrophil aggregation in response to chemotactic peptide activation was mathematically modeled using a Smoluchowski analysis. The kinetics of aggregate formation were fit with a collision kernel which included adhesion efficiency and shear rate. We explored the effect on efficiency by blocking the integrin or selecttn over a range of cell contact durations (At-1 msec to 50 msec). By enzymaticatly cleaving L-selectin with chymotrypsin, or cleaving its ligand with O-siafogyfcoprotein endopeptfdase, we found that L-selectin independent aggregation occurred at G < 200 s-1 (At-16 msec). L-selectin was absolutely required for aggregation at shear rates > BOO s-1 (At4 msec). L-selectin independent adhesion was also quantitated between heterotypic aggregates of activated neutrophils and ICAM-1 transfected cells, and was limited to shear rates <800 s-i. The results are consistent with a sequential mechanism of selectin and integrin mediated adhesion dependent on receptor affinity and cell contact duration.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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