Pertussis toxin-induced lung edema - Role of manganese superoxide dismutase and protein kinase C

The mechanism by which pertussis toxin (Ptx) causes lung edema is not clear . We investigated the role of pulmonary manganese superoxide dismutase (MnS OD) and protein kinase C (PKC) in Ptx-induced lung edema. We demonstrated t hat intraperitoneal injection of Ptx at a concentration of 5 mu g/100 g bod y weight caused a similar degree of lung edema in 2 d, as measured by lung wet weight/dry weight ratio, in heterozygous MnSOD gene (Sod2)-knockout mic e (Sod2(+/-)) and in their wild-type littermates (Sod2(+/+)). The level of lung MnSOD activity in Sod2(+/-) mice was approximately half that of Sod2(/-) mice. Ptx had no effect on levels of lung MnSOD messenger RNA, immunore active protein, or enzyme activity in either Sod2(+/+) or Sod2(+/-) mice. P tx also had no effect on lung copper-zinc SOD, catalase, and glutathione pe roxidase activities in these mice. On the other hand, Ptx caused the activa tion of lung PKC, for example, by translocation of a 72-kD PKC isoform from the cytosolic fraction to the membrane fraction. Pretreatment of mice with bisindolylmaleimide, a PKC inhibitor, prevented both the Ptx-induced activ ation of PKC and lung edema. These data suggest that Ptx-induced lung edema in mice is, at least in part, due to the activation of lung PKC.