Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Endothelial cell adhesion molecule expression in gene-targeted mice
Ist Teil von
American journal of physiology. Heart and circulatory physiology, 1997-10, Vol.273 (4), p.H1903-H1908
Ort / Verlag
United States
Erscheinungsjahr
1997
Quelle
MEDLINE
Beschreibungen/Notizen
1 Department of Molecular and
Cellular Physiology, Louisiana State University Medical Center,
Shreveport, Louisiana 71130;
2 Discovery Research, Pharmacia
and Upjohn Inc., Kalamazoo, Michigan 49001; and
3 Division of
Inflammation/Autoimmune Diseases, Hoffmann-La Roche Inc., Nutley,
New Jersey 07110
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 C57Bl/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- (TNF- ) 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- -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.
2 -integrins; E-selectin; P-selectin; intracellular adhesion molecule-1