Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins

Immunity. 1994 Nov;1(8):709-20. doi: 10.1016/1074-7613(94)90041-8.


The initial rolling interaction of leukocytes with the blood vessel wall during leukocyte trafficking has been postulated to rely on members of the selectin family of adhesion molecules. Two selectins, E-selectin and P-selectin, have been identified that are expressed on activated endothelial cells. Mice deficient in E-selectin expression have been produced in order to examine the role of this selectin in leukocyte trafficking. Mice homozygous for an E-selectin null mutation were viable and exhibited no obvious developmental alterations. E-selectin-deficient mice displayed no significant change in the trafficking of neutrophils in several models of inflammation. However, blocking both endothelial selectins by treatment of the E-selectin-deficient animals with an anti-murine P-selectin antibody, 5H1, significantly inhibited neutrophil emigration in two distinct models of inflammation. While neutrophil accumulation at early times during thioglycollate-induced peritonitis was dependent on P-selectin, neutrophil accumulation at later time points was blocked by 5H1 only in E-selectin-deficient mice but not in wild-type mice. Similarly, edema as well as leukocyte accumulation in a model of delayed-type hypersensitivity in the skin was almost completely prevented by blockade of P-selectin function with 5H1 in the E-selectin-deficient mice while the same treatment had no effect in wild-type mice. These data demonstrate that the majority of neutrophil migration in both models requires an endothelial selectin but that E-selectin and P-selectin are functionally redundant. These data have important implications in the use of selectin antagonists in the treatment of inflammatory disease.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Base Sequence
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / physiology*
  • Chemotaxis, Leukocyte*
  • E-Selectin
  • Female
  • Inflammation / etiology*
  • Kidney / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Genetic
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Myocardium / metabolism
  • Neutrophils / cytology
  • P-Selectin
  • Peritoneum / cytology
  • Platelet Membrane Glycoproteins / biosynthesis
  • Platelet Membrane Glycoproteins / immunology
  • Platelet Membrane Glycoproteins / physiology*
  • Time Factors
  • Vascular Cell Adhesion Molecule-1


  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • E-Selectin
  • P-Selectin
  • Platelet Membrane Glycoproteins
  • Vascular Cell Adhesion Molecule-1