Protection against oxygen toxicity by tracheal insufflation of endotoxin: role of Mn SOD and alveolar macrophages.
Endotoxin and the cytokines, tumor necrosis factor and interleukin-1, are known to protect adult rats against O2 toxicity. However, whether the effect of endotoxin is mediated through its direct effect on lung cells or through cytokines is not clear. In this study, we demonstrated that endotoxin at a dosage of 5 micrograms/rat (14-20 micrograms/kg) attenuated O2-induced pulmonary injury and markedly prolonged the survival of rats exposed to 100% O2. Endotoxin was more protective when given by intratracheal insufflation or intravenous injection than by intraperitoneal injection. The endotoxin-induced O2 tolerance was associated with a selective enhancement of pulmonary manganese superoxide dismutase, but not Cu,Zn SOD, mRNA. In addition, depletion of 84% rat alveolar macrophages by liposome-encapsulated dichloromethylene diphosphonate, resulted in a marked reduction (86%) of endotoxin-induced release of tumor necrosis factor into the alveolar space. However, endotoxin was still protective in these alveolar macrophage-depleted animals.
Tang
G
G
Research Service, Samuel S. Stratton Department of Veterans Affairs Medical Center, Albany, New York 12208.
Berg
J T
JT
White
J E
JE
Lumb
P D
PD
Lee
C Y
CY
Tsan
M F
MF
D000818:Animals; D004731:Endotoxins / Q000008:administration & dosage* / Q000494:pharmacology*; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D010100:Oxygen / Q000037:antagonists & inhibitors / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000502:physiology*; D016019:Survival Analysis
D004731:Endotoxins; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D010100:Oxygen