Antiinflammatory effects of hydrogen peroxide in neutrophil activation and acute lung injury.
BACKGROUND
Although reactive oxygen species (ROS) are generally considered to be proinflammatory and to contribute to cellular and organ dysfunction when present in excessive amounts, there is evidence that specific ROS, particularly hydrogen peroxide (H(2)O(2)), may have antiinflammatory properties.


OBJECTIVE
To address the role that increases in intracellular H(2)O(2) may play in acute inflammatory processes, we examined the effects of catalase inhibition or the absence of catalase on LPS-induced inflammatory responses.


METHODS
Neutrophils from control or acatalasemic mice, or control neutrophils incubated with the catalase inhibitor aminotriazole, were treated with LPS, and levels of reactive oxygen species, proteasomal activity, NF-kappaB activation, and proinflammatory cytokine expression were measured. Acute lung injury (ALI) was produced by intratracheal injection of LPS into control, acatalasemic-, or aminotriazole-treated mice.


RESULTS
Intracellular levels of H(2)O(2) were increased in acatalasemic neutrophils and in neutrophils exposed to aminotriazole. Compared with LPS-stimulated neutrophils from control mice, neutrophils from acatalasemic mice or neutrophils treated with aminotriazole demonstrated reduced 20S and 26S proteasomal activity, IkappaB-alpha degradation, NF-kappaB nuclear accumulation, and production of the proinflammatory cytokines TNF-alpha and macrophage inhibitory protein (MIP)-2. The severity of LPS-induced ALI was less in acatalasemic mice and in mice treated with aminotriazole as compared with that found in control mice.


CONCLUSIONS
These results indicate that H(2)O(2) has antiinflammatory effects on neutrophil activation and inflammatory processes, such as ALI, in which activated neutrophils play a major role.
Zmijewski
Jaroslaw W
JW
Department of Medicine, University of Alabama at Birmingham School of Medicine, 1530 3rd Avenue S, Birmingham, AL 35294-0012, USA.
Lorne
Emmanuel
E
Zhao
Xia
X
Tsuruta
Yuko
Y
Sha
Yonggang
Y
Liu
Gang
G
Abraham
Edward
E
D020642:Acatalasia / Q000276:immunology / Q000378:metabolism; D055371:Acute Lung Injury / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000276:immunology / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D000640:Amitrole