Heterogeneity of Expression of E- and P-Selectins In Vivo

A novel technique involving radiolabeled monoclonal antibodies was used to characterize and compare the expression of E- and P-selectin on unstimulated, histamine-challenged, and endotoxin-challenged endothelial cells in various tissues of the mouse. Under unstimulated conditions, E-selectin was abs...

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Bibliographic Details
Published in:Circulation research 1996-09, Vol.79 (3), p.560-569
Main Authors: Eppihimer, Michael J, Wolitzky, Barry, Anderson, Donald C, Labow, Mark A, Granger, D. Neil
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal
Biological and medical sciences
Blood vessels and receptors
E-Selectin - genetics
E-Selectin - metabolism
Fundamental and applied biological sciences. Psychology
Gene Deletion
Histamine - pharmacology
Lipopolysaccharides - pharmacology
Male
Mice
Mice, Inbred C57BL
P-Selectin - genetics
P-Selectin - metabolism
Vertebrates: cardiovascular system
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Summary:A novel technique involving radiolabeled monoclonal antibodies was used to characterize and compare the expression of E- and P-selectin on unstimulated, histamine-challenged, and endotoxin-challenged endothelial cells in various tissues of the mouse. Under unstimulated conditions, E-selectin was absent in all organs, but significant expression of P-selectin was observed in several organs. Histamine induced a rapid time-dependent upregulation of P-selectin, with the largest responses observed in mesentery and lung. Significant fold elevations in P-selectin expression occurred as early as 5 minutes after the histamine injection and remained elevated up to 1 hour. Histamine-induced P-selectin upregulation was inhibited by the H1 receptor antagonist diphenhydramine, whereas the H2 receptor antagonist cimetidine had no effect. Endotoxin (lipopolysaccharide [LPS]) also induced a time-dependent expression of P-selectin that reached a maximum between 4 and 8 hours after endotoxin administration. LPS-induced upregulation of P-selectin was greatest in heart and stomach, which exhibited insignificant constitutive expression of P-selectin. LPS also induced a time-dependent upregulation of E-selectin, with maximal expression occurring 3 to 5 hours after intraperitoneal administration. The lung and small intestine exhibited the largest responses to LPS challenge. Histamine administration did not affect E-selectin expression in any tissue. E- and P-selectin-deficient mice were used to test the specificity of monoclonal antibody binding in unstimulated, histamine-challenged, and LPS-stimulated tissues. Vascular binding of the radiolabeled E-selectin and P-selectin monoclonal antibodies was not observed in the respective deficient mice. These findings suggest that P-selectin is constitutively expressed on vascular endothelium in some tissues of the mouse and that there are significant regional differences in the magnitude and time course of histamine- and endotoxin-induced P-selectin expression. In contrast, E-selectin appears to be absent on unstimulated vascular endothelium but is upregulated within 3 hours after the administration of endotoxin in most tissues.(Circ Res. 1996;79:560-569.)
ISSN:0009-7330
1524-4571
DOI:10.1161/01.res.79.3.560