Induction of LFA-1-dependent neutrophil rolling on ICAM-1 by engagement of E-selectin

Microcirculation. 2006 Mar;13(2):99-109. doi: 10.1080/10739680500466376.


Objective: To study rolling of mouse neutrophils on E-selectin and ICAM-1 in an ex vivo flow chamber system.

Methods: The authors developed a small autoperfused flow chamber (20 x 200-microm cross section) that allows direct visualization of cells with and without fluorescent labeling and does not require recirculation of blood.

Results: Neutrophils rolled on E-selectin alone, but were unable to interact with immobilized ICAM-1. When ICAM-1 was co-immobilized with E-selectin, the number of cells that rolled was doubled, but no significant firm adhesion was observed. This phenomenon was specific for E-selectin, and no enhancement of rolling was observed when P-selectin was immobilized with ICAM-1. The increased neutrophil rolling seen on E-selectin and ICAM-1 substrates required beta2 integrins. Treating mice with antibodies to the beta2 integrins LFA-1 and Mac-1 showed that LFA-1 was primarily responsible for mediating rolling on ICAM-1 in this model. Increased rolling on E-selectin and ICAM-1 was significantly reduced following administration of a specific p38 mitogen-activated protein kinase (MAPK) inhibitor.

Conclusion: The data show that neutrophil rolling on E-selectin leads to partial activation of LFA-1, enabling LFA-1-dependent rolling on ICAM-1. This mechanism is likely to amplify and accelerate neutrophil recruitment in inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • E-Selectin / metabolism*
  • Inflammation / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Leukocyte Rolling / physiology*
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Mice
  • Mice, Transgenic
  • Neutrophils / cytology
  • Neutrophils / physiology*


  • E-Selectin
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1