Reactive oxygen species (ROS), including
superoxide anions, play an important role in mediating
acute lung injury. We examined whether
polyethylene glycol-conjugated
superoxide dismutase (
PEG-SOD) attenuates
lung injury in Escherichia coli-treated guinea pigs. Twenty-four guinea pigs were divided into four groups: (1) control group; (2) septic group, in which live E. coli (2 x 10(9)/kg) were injected intravenously; (3) pretreatment group, in which
PEG-SOD (2,000 IU/kg) was injected intravenously 15 min before E. coli; and (4) posttreatment group, in which
PEG-SOD (2,000 IU/kg) was injected intravenously 30 min after E. coli.
Lung injury was assessed by the concentration ratio of 125I-labeled
albumin in lung tissue and bronchoalveolar lavage (BAL) fluid relative to plasma (L/P and BAL/P),
lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid. Plasma half-life of
PEG-SOD in normal guinea pigs was 13.5 h. L/P,
lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid decreased in both pretreatment and posttreatment groups compared with the septic group. BAL/P decreased in the pretreatment group but not in the posttreatment group compared with the septic group. After the animal model studies, we investigated the effect of
PEG-SOD on the human neutrophil extracellular generation of ROS stimulated by
phorbol myristate acetate (PMA) in
lucigenin-dependent chemiluminescence (CL).
PEG-SOD at concentrations greater than or equal to 0.1 U/ml inhibited PMA-induced CL in a dose-dependent manner. We also examined the effect of
PEG-SOD on the neutrophil intracellular generation of ROS using flow cytometry to assess intracellular
hydroethidine oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)