title: Burn-Evoked Reactive Oxygen Species Immediately After Injury are Crucial to Restore the Neutrophil Function Against Postburn Infection in Mice.
abstract: Although reactive oxygen species (ROS) basically play beneficial roles to maintain host homeostasis against external disturbance/stress including infection, excessive ROS generation by activated neutrophils can sometimes cause organ damage. We investigated the role of burn-induced ROS generation in the injured hosts, focusing on postburn infection. C57BL/6 mice received a 20% full-thickness burn injury. In these mice, the burn-induced ROS generation was inhibited during and immediately after injury by pretreatment with superoxide dismutase (at 1 h before and immediately before injury), or the subsequent ROS production was inhibited posttreatment with superoxide dismutase (at 1 and 2 h after injury), which could not scavenge the ROS produced immediately after injury. As expected, inhibition of ROS production during/immediately after injury reduced the burn-induced pulmonary damage at 6 h, whereas inhibition of the subsequent ROS production did not lead to any improvements. Burn injury rendered the mice susceptible to bacterial infection at 5 days after injury and impaired bactericidal activity of neutrophils. Nevertheless, inhibition of the ROS production during/immediately after injury did not improve the burn-induced susceptibility to infection or the neutrophil dysfunction. Interestingly, inhibition of the subsequent ROS production potently restored the neutrophil functions and hematopoietic function of the bone marrow myelocytes, thereby improving the postburn infection. Thus, although the inhibition of burn-evoked ROS generation is effective against burn-induced organ injury, it may be ineffective against postburn infection. Preservation of the immediate burn-evoked ROS production, but the inhibition of subsequent ROS production, may be crucial to protect against postburn infection.
authors.affiliation: *Division of Traumatology, Research Institute, and †Department of Immunology and Microbiology, National Defense Medical College, Saitama; and ‡Division of Critical Care Medicine, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ono
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Daizoh
authors.initials: D
authors.lastname: Saitoh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002056:Burns / Q000097:blood / Q000150:complications / Q000276:immunology*; D004927:Escherichia coli Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000097:blood*; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D019009:Proto-Oncogene Proteins c-kit