Autoperfused mouse flow chamber reveals synergistic neutrophil accumulation through P-selectin and E-selectin

J Leukoc Biol. 2004 Nov;76(5):985-93. doi: 10.1189/jlb.1003483. Epub 2004 Apr 1.

Abstract

To study rolling of mouse neutrophils on P- and E-selectins in whole blood and without cell isolation, we constructed an autoperfused flow chamber made from rectangular microslides (0.2x2 mm) perfused from a carotid artery catheter. A differential pressure transducer served to measure wall shear stress. Green fluorescent neutrophils rolled on P-selectin but not E-selectin coated at 50 ng/ml, with some rolling on E-selectin at 150 ng/ml. However, when P- and E-selectins were coimmobilized, the resulting number of rolling neutrophils was sixfold and fourfold higher than on P- or E-selectin alone. Velocity and flux analysis shows that P-selectin initiates neutrophil rolling, and a small amount of E-selectin, unable to capture many neutrophils, reduces the rolling velocity of all neutrophils by more than 90%. The unexpected synergism between E- and P-selectins explains why neutrophil recruitment is enhanced when both selectins are expressed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Diffusion Chambers, Culture / instrumentation
  • Diffusion Chambers, Culture / methods
  • Drug Synergism
  • E-Selectin / metabolism*
  • E-Selectin / pharmacology
  • Green Fluorescent Proteins
  • Leukocyte Rolling / drug effects
  • Leukocyte Rolling / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • P-Selectin / metabolism*
  • P-Selectin / pharmacology
  • Stress, Mechanical
  • Transducers, Pressure

Substances

  • E-Selectin
  • P-Selectin
  • Green Fluorescent Proteins