Inhaled nitric oxide attenuates acute lung injury via inhibition of nuclear factor-kappa B and inflammation.
The effect of inhaled nitric oxide (NO) on inflammatory process in acute lung injury (ALI) is unclear. The aims of this study were to 1) examine whether inhaled NO affects the biochemical lung injury parameters and cellular inflammatory responses and 2) determine the effect of inhaled NO on the activation of nuclear factor-kappa B (NF-kappa B) in lipopolysaccharide (LPS)-induced ALI. Compared with saline controls, rabbits treated intravenously with LPS showed increases in total protein and lactate dehydrogenase in the bronchoalveolar lavage (BAL) fluid, indicating ALI. LPS-treated animals with NO inhalation (LPS-NO) showed significant decreases in these parameters. Neutrophil numbers in the BAL fluid, the activity of reactive oxygen species in BAL cells, and the levels of interleukin (IL)-1 beta and IL-8 in alveolar macrophages were increased in LPS-treated animals. In contrast, neutrophil numbers and these cellular activities were substantially decreased in LPS-NO animals, compared with LPS-treated animals. NF-kappa B activation in alveolar macrophages from LPS-treated animals was also markedly increased, whereas this activity was effectively blocked in LPS-NO animals. These results suggest that inhaled NO attenuates LPS-induced ALI and pulmonary inflammation. This attenuation may be associated with the inhibition of NF-kappa B activation.
Kang
Jihee Lee
JL
Division of Cell Biology, Department of Physiology, College of Medicine, Ewha Medical Research Center, Ewha Women's University, Seoul 158-056, Korea.
Park
Wann
W
Pack
In Soon
IS
Lee
Hui Su
HS
Kim
Mi Jung
MJ
Lim
Chae-Man
CM
Koh
Younsuck
Y
D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011506:Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase