Endothelial cell adhesion molecule expression in gene-targeted mice.
Gene-targeted mice are now routinely employed as tools for defining the contribution of different leukocyte and endothelial cell adhesion molecules to the leukocyte recruitment and tissue injury associated with acute and chronic inflammation. The objective of this study was to determine whether gene-targeted mice that are deficient in CD11/CD18, intracellular adhesion molecule-1 (ICAM-1), or P-selectin exhibit an altered constitutive or induced expression of the endothelial cell adhesion molecules E- and P-selectin. The gene-targeted mice were all developed in the 129Sv mouse strain and backcrossed into C57B1/6J mice. The number of backcrosses ranged between 8 (P-selectin) and 10 (CD18 and ICAM-1) generations. The dual-radiolabeled monoclonal antibody technique was used to quantify E- and P-selectin expression in different vascular beds. In the unstimulated state, E-selectin expression was significantly elevated (relative to wild-type mice) in the stomach, large intestine, and brain of mutants deficient in ICAM-1. In general, constitutive expression of P-selectin did not differ between wild-type, ICAM-1-deficient, and CD11/CD18-deficient mutants. In CD11/CD18-deficient mice, tumor necrosis factor-alpha (TNF-alpha) administration elicited a more profound upregulation of P-selectin in several vascular beds, compared with wild-type and ICAM-1-deficient mice. E-selectin expression in brain of TNF-alpha-stimulated, ICAM-1-deficient, and P-selectin-deficient mice was attenuated compared with wild-type mice. These findings indicate that chronic deficiency of some of the adhesion glycoproteins that mediate leukocyte recruitment alters basal and induced surface expression of other adhesion molecules on endothelial cells.
Eppihimer
M J
MJ
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130-3932, USA.
Russell
J
J
Anderson
D C
DC
Wolitzky
B A
BA
Granger
D N
DN
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D018845:CD11 Antigens / Q000235:genetics; D018821:CD18 Antigens / Q000235:genetics; D019040:E-Selectin / Q000378:metabolism*; D018390:Gene Targeting; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018845:CD11 Antigens; D018821:CD18 Antigens; D019040:E-Selectin; D019007:P-Selectin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1