First Author | Tsan MF | Year | 1999 |
Journal | Am J Respir Cell Mol Biol | Volume | 20 |
Issue | 3 | Pages | 465-73 |
PubMed ID | 10030845 | Mgi Jnum | J:114242 |
Mgi Id | MGI:3688654 | Doi | 10.1165/ajrcmb.20.3.3373 |
Citation | Tsan MF, et al. (1999) Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C. Am J Respir Cell Mol Biol 20(3):465-73 |
abstractText | The mechanism by which pertussis toxin (Ptx) causes lung edema is not clear. We investigated the role of pulmonary manganese superoxide dismutase (MnSOD) and protein kinase C (PKC) in Ptx-induced lung edema. We demonstrated that intraperitoneal injection of Ptx at a concentration of 5 microg/100 g body 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 mice (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, immunoreactive protein, or enzyme activity in either Sod2(+/+) or Sod2(+/-) mice. Ptx also had no effect on lung copper-zinc SOD, catalase, and glutathione peroxidase activities in these mice. On the other hand, Ptx caused the activation 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 activation 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. |