Neutrophil aggregation mediated by β2-integrin and ICAM-3 at low hydrodynamic shear

Scott I. Simon, Andrew Taylor, Sriram Neelamegham, J. David Hellums, C. Wayne Smith

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Leukocytes target to sites of vascular inflammation by formation of specific molecular bonds which overcome the hydrodynamic forces of flowing blood. Current data support a mechanism of leukocyte margination by which selectins rapidly bind and dissociate from glycoprotein ligands, thereby mediating transient adhesion. Subsequently, cell activation by chemotactic factors activates β2-integrin receptors Mac-1 and LFA-1 which mediate firm adhesion. Neutrophils can also be captured in shear flow through L-selectin tethering an apposing neutrophil. Homotypic neutrophil aggregation stimulated by chemotactic peptide results in stable adhesion. Analogous to leukocyte margination in the vasculature, neutrophil capture requires L-selectin and β2-integrin at physiologic shear rates. Using cone plate viscometry to apply uniform shear rates (G) and flow cytometry to quantitate aggregate formation, we have recently reported that optimal adhesion efficiency occurs only over a relatively narrow range of G between 400 and 800 s-1 (Taylor et al., Biophys. J., 1996). In the current studies we demonstrate that at G < 200s-1 adhesion becomes independent of L-selectin and is supported by three adhesion molecules, LFA-1, Mac-1, and ICAM-3. Adhesion at G = 100s-1 occurred with an efficiency of ∼20%, and was inhibited by ∼40% in the presence of mAbs to either of the three receptor types. The data support a mechanism in which LFA-1 binds to ICAM-3 within seconds of stimulation and maintains aggregate adhesion only over the initial 1-2 m. Mac-1 also supports adhesion within seconds of stimulation but maintained aggregates over a longer duration.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

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

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