Pulmonary influxed neutrophils have been suggested to be involved in the development of
hyperoxia-induced
lung injury. We recently revealed that a highly toxic substance,
9,10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named
leukotoxin. Because
hyperoxia-induced
lung injury is a model of
adult respiratory distress syndrome (ARDS), this study was designed to investigate whether or not
leukotoxin is involved in the genesis of pulmonary
oxygen toxicity and ARDS. After exposure to
hyperoxia for 60 h, rats showed acute
pulmonary edema, which was evidenced by increased lung weight,
albumin concentrations, and
angiotensin-converting enzyme (ACE) activities in lung lavages. These changes were correlated with an increased number of neutrophils. We detected
leukotoxin in lung lavages of rats after exposure to
hyperoxia for 60 h by high performance liquid chromatography and gas-chromatography/mass spectrometry. After
intravenous injection of
leukotoxin (100 mumol/kg) to rats, acute edematous
lung injury occurred showing increases in lung weight, lung lavage
albumin concentrations, and lung lavage ACE activities. In the lung lavages obtained from 5 patients with ARDS, significant increases in
albumin concentrations and ACE activities were observed compared with those from subjects without
pulmonary disease. Moreover, considerable amounts of
leukotoxin, 38.5 +/- 21.9 nmol/lung lavage, were observed in the lavages from patients with ARDS. These findings suggest that
leukotoxin plays an important role in the genesis of acute edematous lung damage in pulmonary
oxygen toxicity, and that
leukotoxin also links with the development of
lung injury observed in patients with ARDS.