We have observed that neutrophils biosynthesize
linoleate epoxide,
9,10-epoxy-12-octadecenoate, and have named it
leukotoxin because of its cytotoxic effect. In this experiment, the effect of
leukotoxin on the lung was investigated. Acute effect of
leukotoxin: Using Wistar rats,
leukotoxin (100 mumol/kg) was injected intravenously for the
leukotoxin group, and
linoleate (100 mumol/kg) for the
linoleate group. Physiological saline was injected as the control. Ten min after injection, rats were divided into 3 groups: (1) lungs were isolated, and
lung wet weight, and dry weight were measured; (2) lung lavages were performed, and
albumin concentration and activity of
angiotensin converting enzyme (ACE) were measured; (3) morphological changes were studied by light and electron microscope. After administration of
leukotoxin,
lung wet weight/body weight ratios and dry weight/wet weight ratios were increased.
Albumin concentration and ACE activity in lung lavages were also increased.
Pulmonary edema was also confirmed by light microscopic findings. Alveolar epithelial cell damage and endothelium damage were also observed.
Linoleate had no significant effect on these biochemical parameters and morphological findings. Subacute effect of
leukotoxin: Twelve hr after administration of
leukotoxin (50 mumol/kg) or
linoleate (50 mumol/kg), the same studies were performed as in the acute experiments. Immediately after administration of
leukotoxin, no significant effect was observed. However, 12 hr later similar changes were observed as in the acute experiments.
Linoleate did not show any significant effect 12 hr after injection. These results indicate that
leukotoxin biosynthesized by neutrophils might be closely related to the genesis of inflammatory
edema.