title: Antiinflammatory effects of hydrogen peroxide in neutrophil activation and acute lung injury.
abstract: 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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham School of Medicine, 1530 3rd Avenue S, Birmingham, AL 35294-0012, USA.
authors.forename: Jaroslaw W
authors.initials: JW
authors.lastname: Zmijewski
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lorne
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuruta
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Sha
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
mesh_terms: 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
chemical_list: 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