CHARACTERIZATION OF E-SELECTIN-DEFICIENT MICE - DEMONSTRATION OF OVERLAPPING FUNCTION OF THE ENDOTHELIAL SELECTINS

被引:341
作者
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
机构
[1] GLAXO INC,RES INST,DEPT CELL PHYSIOL,RES TRIANGLE PK,NC 27709
[2] ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,MELBOURNE,VIC 3050,AUSTRALIA
[3] ROCHE INST MOLEC BIOL,NUTLEY,NJ 07110
关键词
D O I
10.1016/1074-7613(94)90041-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页码:709 / 720
页数:12
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