Cooperativity between selectins and β 2-integrins define neutrophil capture and stable adhesion in shear flow

Daniel B. Mcdonough, Fiona A. Mcintosh, Constantina Spanos, Sriram Neelamegham, Harry L. Goldsmith, Scott I. Simon

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

A cooperative, sequential process of molecular recognition governs leukocyte capture, rolling, and arrest on inflamed endothelium. Flowing neutrophils are captured via heterotypic adhesive interactions mediated by endothelial E-selectin, whereas homotypic interactions between neutrophils are mediated by L-selectin. To elucidate how each selectin facilitates the transition to CD18-mediated stable adhesion, E-selectin and L-selectin were expressed at defined site density in a murine pre-B-cell line. Direct observation of two-body collisions revealed that 30% of neutrophil interactions with E-selectin transfectants formed doublets at low shear rate G = 14 s -1 whereas a threshold shear rate 14 s -1 ≤ G ≤ 110 s -1 was necessary for L-selectin adhesion. Adhesion via L-selectin resisted rupture at high shear stress, while E-selectin tethered doublets remained intact longer once formed. Moreover, higher expression of L-selectin (1100 sites/μm 2) than that of E-selectin (220 sites/μm 2) was required for comparable heterotypic adhesion efficiency. With a threefold rise in active CD 18 upregulated on chemotactically stimulated neutrophils, homotypic adhesion efficiency increased 10-fold compared to less than 5-fold for heterotypic adhesion to selectin transfectants. Coexpression of E-selectin and ICAM-1 boosted adhesion efficiency threefold more than either receptor alone over the range of active CD 18 expression. These data are the first to quantify adhesion efficiency mediated by selectin tethering and conformational activation of β 2-integrin in neutrophils in shear flow.

Original languageEnglish (US)
Pages (from-to)1179-1192
Number of pages14
JournalAnnals of Biomedical Engineering
Volume32
Issue number9
DOIs
StatePublished - Sep 2004

Keywords

  • Cell adhesion
  • Efficiency
  • Integrin
  • Selectin
  • Shear stress
  • Viscometry

ASJC Scopus subject areas

  • Biomedical Engineering

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