CHARACTERIZATION OF E-SELECTIN-DEFICIENT MICE - DEMONSTRATION OF OVERLAPPING FUNCTION OF THE ENDOTHELIAL SELECTINS
- Author(s)
- LABOW, MA; NORTON, CR; RUMBERGER, JM; LOMBARDGILLOOLY, KM; SHUSTER, DJ; HUBBARD, J; BERTKO, R; KNAACK, PA; TERRY, RW; HARBISON, ML; Kontgen, F; STEWART, CL; MCINTYRE, KW; WILL, PC; BURNS, DK; WOLITZKY, BA;
- Details
- Publication Year 1994-11,Volume 1,Issue #8,Page 709-720
- Journal Title
- IMMUNITY
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- CELL PRESS
- Keywords
- LEUKOCYTE-ADHESION MOLECULE-1; CELL-ADHESION; P-SELECTIN; LUNG INJURY; STEM-CELLS; T-CELLS; NEUTROPHILS; RECEPTOR; EXPRESSION; RECOGNITION
- Publisher's Version
- https://doi.org/10.1016/1074-7613(94)90041-8
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- Refer to copyright notice on published article.
Creation Date: 1994-11-01 12:00:00