Hypoxic stress alone does not modulate endothelial surface expression of bovine E-selectin and intercellular adhesion molecule-1 (ICAM-1).
Hypoxemia is a common event in many vascular diseases, especially vascular ischemia. Since endothelial cells of blood vessels are exposed to conditions within the vascular space and leucocytes play a key role in ischemia/reperfusion injury, we hypothesized that endothelial exposure to hypoxia may regulate expression of surface proteins important in leucocyte-endothelial interactions, such as E-selectin and intercellular adhesion molecule (ICAM-1). In this study, we used isolated bovine aortic endothelial monolayers to examine endothelial surface alterations of E-selectin and ICAM-1 induced by tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS) and hypoxia using a whole cell enzyme-linked immunosorbent assay (ELISA). Bovine endothelial exposure to TNF-alpha (50 ng/mL) induced a time dependent increase (range 0-24h) in specific E-selection surface expression. Endothelial exposure to hypoxia alone (pO2 approximately 3 mmHg, range 0-24 h), however, failed to elicit endothelial E-selectin expression. Endothelial exposure to LPS brought about a dose- and time-dependent (range 0.5 ng/mL and 2-8 h) increase in specific ICAM-1 surface expression (max. 3.5 +/- 0.15-fold increase over no cytokine control at 10 ng/mL, 4 h). Hypoxia (pO2 approximately 3 mmHg, 8h), however, did not induce ICAM-1 surface expression over normoxia levels.


CONCLUSIONS
i) bovine endothelial E-selectin and ICAM-1 surface expression are regulated molecules, ii) hypoxia, per se, does not regulate surface expression of either E-selectin or ICAM-1. These results suggest that hypoxic endothelia may require additional external signals for generation of adaptive inflammatory responses.
Zünd
G
G
Department of Anesthesia, Ischemia/Reperfusion Center, Brigham and Women's Hospital, Boston, MA 02115, USA.
Dzus
A L
AL
McGuirk
D K
DK
Breuer
C
C
Shinoka
T
T
Mayer
J E
JE
Colgan
S P
SP
D000818:Animals; D002417:Cattle; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D000860:Hypoxia / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019040:E-Selectin; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1