It is well known that neutrophils are involved in the inflammatory process. Although neutrophils are the most important factor in preventing bacterial infection, the adverse effects of neutrophils on the cellular function are also recognized. We recently revealed that a highly toxic substance, 9, 10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named leukotoxin. This study was designed to investigate whether or not leukotoxin is involved in the genesis of pulmonary oxygen toxicity and adult respiratory distress syndrome (ARDS) . Experimental study: 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. Neutrophil recruitment in lung lavages was observed. Leukotoxin was also detected in lung lavages of rats after exposure to hyperoxia for 60 h. Intravenous injection of leukotoxin (100μmol/kg) caused acute edematous lung injury. Clinical study: 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 diseases. Moreover, considerable amounts of leukotoxin were observed in lung lavages from patients with ARDS.
Hence, these results indicate that leukotoxin biosynthesized by neutrophlis might be closely related to the genesis of pulmonary oxygen toxicity and lung injury observed in patients with ARDS.