Existence of leukotoxin 9,10-epoxy-12-octadecenoate in lung lavages from rats breathing pure oxygen and from patients with the adult respiratory distress syndrome.
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.
Ozawa
T
T
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Sugiyama
S
S
Hayakawa
M
M
Satake
T
T
Taki
F
F
Iwata
M
M
Taki
K
K
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis* / Q000166:cytology; D004195:Disease Models, Animal; D005098:Exotoxins / Q000032:analysis* / Q000502:physiology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008041:Linoleic Acids / Q000032:analysis*; D009504:Neutrophils; D010100:Oxygen / Q000633:toxicity*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D005098:Exotoxins; D008041:Linoleic Acids; C018579:leukotoxin; C051208:9,10-epoxy-12-octadecenoic acid; D010100:Oxygen