It is well known that pulmonary influx of neutrophils is involved in
lung injury in patients with
adult respiratory distress syndrome (ARDS). Neutrophils are major contributors to the self-defence mechanism, however, adverse effects of neutrophils have also been recognized. Recently, we found that a highly toxic substance, 9, 10-epoxy-12-octadecenoate (
leukotoxin) is biosynthesized by human neutrophils. This study was designed to investigate whether or not
leukotoxin participates in
lung injury in ARDS and coagulation abnormality which is often associated with ARDS.
Intravenous injection of
leukotoxin (100 mumol/kg) caused acute edematous
lung injury, which was evidenced by increased lung weight,
albumin concentrations, and
angiotensin converting enzyme activities in lung lavages. Pulmonary capillary endothelial damage and
pulmonary edema were observed by electron microscopy. Moreover, considerable amounts of
leukotoxin were detected in lung lavage fluid of rats exposed to pure
oxygen for 60 h and patients with ARDS. An increased number of neutrophils and
albumin concentrations were also observed in these lavage fluids.
Intravenous injection of
leukotoxin (100 mumol/kg) induced coagulation abnormalities such as
disseminated intravascular coagulation. Increased levels of plasma
leukotoxin were detected in ARDS patients with coagulation abnormalities. These results suggest that
leukotoxin biosynthesized by neutrophils is an important contributor to
lung injury in ARDS and associated coagulation abnormalities.