Cytokine-induced VCAM-1 and ICAM-1 expression in different organs of the mouse.
The dual radiolabeled mAb technique was used to quantify the constitutive and induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the microvasculature of different organs of the mouse. The constitutive expression of both adhesion molecules varied significantly between tissues, with ICAM-1 levels consistently higher than VCAM-1 in all tissues studied. Following systemic administration of endotoxin (LPS), an increased surface expression of both adhesion molecules occurred in most organs, with the largest increases for ICAM-1 (2 to 3x increase) noted in the heart, small intestine, and brain, while heart and small intestine exhibited the largest increases in LPS-induced VCAM-1 expression (2 to 5x increase). These responses occurred in the face of an unaltered expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) in all tissues. TNF-alpha also elicited an increased expression of both adhesion molecules, with initial increases noted at 2 to 5 h, peak levels at 5 to 9 h, and a sustained elevation above baseline at 24 h. The TNF-alpha-induced increases in both ICAM-1 and VCAM-1 were dose dependent, with significant up-regulation noted at 5 microg/kg and maximal increases occurring at 10 to 25 microg/kg. These studies indicate that while there are significant quantitative differences in constitutive and induced expression of murine ICAM-1 and VCAM-1, the kinetics and dose-response characteristics of the two adhesion molecules to TNF-alpha are qualitatively similar.
Henninger
D D
DD
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130, USA.
Panés
J
J
Eppihimer
M
M
Russell
J
J
Gerritsen
M
M
Anderson
D C
DC
Granger
D N
DN
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000737:chemistry
D016207:Cytokines; D008070:Lipopolysaccharides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1