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Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

¹ Department of Medicine, ² Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama; ³ INSERM ERI-12, Amiens, France

Correspondence and requests for reprints should be addressed to Edward Abraham, M.D., Department of Medicine, University of Alabama at Birmingham School of Medicine, BDB 420, 1530 3rd Avenue S, Birmingham, AL 35294-0012. E-mail: eabraham{at}uab.edu

Rationale: 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 (H₂O₂), may have antiinflammatory properties.

Objectives: To address the role that increases in intracellular H₂O₂ 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-B 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.

Measurements and Main Results: Intracellular levels of H₂O₂ 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, IB- degradation, NF-B nuclear accumulation, and production of the proinflammatory cytokines TNF- 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 H₂O₂ has antiinflammatory effects on neutrophil activation and inflammatory processes, such as ALI, in which activated neutrophils play a major role.

Key Words: reactive oxygen species • neutrophils catalase • LPS • NF-B • acute lung injury

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Reactive oxygen species are generally thought to have proinflammatory effects. However, recent studies suggest that different reactive oxygen intermediates may have distinct effects on cellular activation. What This Study Adds to the Field These results indicate that H2O2 has antiinflammatory effects on neutrophil activation and inflammatory processes, such as ALI, in which activated neutrophils play a major role.

 

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