Publication in detail

Immunity. 1994 Nov;1(8):709-20.

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

Labow, MA; Norton, CR; Rumberger, JM; Lombard-Gillooly, KM; Shuster, DJ; Hubbard, J; Bertko, R; Knaack, PA; Terry, RW; Harbison, MJ; Kontgen, F; Stewart, CL; McIntyre, KW; Will, PC; Burns, DK; Wolitzky, BA

Roche Research Center, Hoffmann-La Roche, Incorporated, New Jersey 07110-1199, USA.

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.

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