Neutrophils have been implicated in multiple models of end-organ injury. The purposes of this study were to determine whether (1) a sublethal septic insult promotes lung neutrophil accumulation, (2) this pulmonary neutrophil accumulation is reversible, (3) these accumulated neutrophils can be activated to injure lung, and (4) this pulmonary neutrophil accumulation obligates lung injury. Rats were administered low-dose endotoxin, 500 μg/kg, intraperitoneally, and at 6 or 12 hours, lungs were harvested and assayed for myeloperoxidase, a marker of neutrophil accumulation, and iodine 125-labeled albumin uptake, a marker of lung injury. A second set of rats were administered low-dose endotoxin and at 6 or 12 hours were given a neutrophil activator formyl-norleucyl-leucyl-phenylalanine (FNLP) 250 μg/kg, intravenously. At 8 or 14 hours, lungs were harvested and assayed for 125I-labeled albumin uptake. A third set of rats were administered low-dose endotoxin, and at 5 1/2 hours, 30 minutes before FNLP administration, they were given a neutrophil elastase inhibitor, methoxoxysuccinyl-L-ananine-L-alanine-L-proline-L-valine-chloromethyl ketone, 2.5 mg/kg, intraperitoneally. At 6 hours rats were given FNLP, at at 8 hours lungs were harvested and assayed for 125I-labeled albumin uptake. The following results were obtained: (1) low-dose endotoxin caused a transient increase (p <0.05) in lung neutrophil accumulation at 6 hours, which was resolved by 12 hours; (2) lung 125I-labeled albumin uptake was unchanged both 6 and 12 hours after isolated low-dose endotoxin administration; (3) neutrophil activation increased (p <0.05) lung 125I-labeled albumin uptake when imposed 6 but not 12 hours after low-dose endotoxin administration; (4) elastase inhibition decreased (p <0.05) the lung 125I-labeled albumin uptake promoted by endotoxin and FNLP. We conclude that sublethal endotoxemia causes a reversible lung neutrophil accumulation and that this lung neutrophil accumulation does not obligate lung injury; but activation of these accumulated neutrophils can promote lung injury, and this neutrophil-associated lung injury is mediated in part by neutrophil elastase.
|Original language||English (US)|
|Number of pages||7|
|Publication status||Published - 1990|
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