Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS.
Hyperbaric oxygen (HBO) is being studied as a therapeutic intervention for ischemia/reperfusion (I/R) injury. We have developed an in vitro endothelial cell model of I/R injury to study the impact of HBO on the expression of intercellular adhesion molecule-1 (ICAM-1) and polymorphonuclear leukocyte (PMN) adhesion. Human umbilical vein endothelial cell (HUVEC) and bovine aortic endothelial cell (BAEC) induction of ICAM-1 required simultaneous exposure to both hypoxia and hypoglycemia as determined by confocal laser scanning microscopy, ELISA, and Western blot. HBO treatment reduced the expression of ICAM-1 to control levels. Adhesion of PMNs to BAECs was increased following hypoxia/hypoglycemia exposure (3. 4-fold, P < 0.01) and was reduced to control levels with exposure to HBO (P = 0.67). Exposure of HUVECs and BAECs to HBO induced the synthesis of endothelial cell nitric oxide synthase (eNOS). The NOS inhibitor nitro-L-arginine methyl ester attenuated HBO-mediated inhibition of ICAM-1 expression. Our findings suggest that the beneficial effects of HBO in treating I/R injury may be mediated in part by inhibition of ICAM-1 expression through the induction of eNOS.
Buras
J A
JA
Department of Emergency Medicine, Brigham and Women's Hospital, Boston 02115, Massachusetts, USA. jburas@massmed.org
Stahl
G L
GL
Svoboda
K K
KK
Reenstra
W R
WR
D000818:Animals; D001011:Aorta / Q000166:cytology; D015153:Blotting, Western; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006931:Hyperbaric Oxygenation; D007003:Hypoglycemia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D018613:Microscopy, Confocal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D004791:Enzyme Inhibitors; D018799:Intercellular Adhesion Molecule-1; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester