Gene therapy for oxidant injury-related diseases: Adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury

Claire Danel, Serpil C. Erzurum, Paule Prayssac, N. Tony Eissa, Ronald Crystal, Philippe Hervé, Bruno Baudet, Michel Mazmanian, Patricia Lemarchand

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector encoding human superoxide dismutase (CuZn-SOD) or catalase cDNA, a mixture of both Ad vectors, or a control Ad vector containing no exogenous gene. Expression of human catalase and CuZn-SOD was demonstrated 3 days later in distal lung epithelial cells and alveolar macrophages, using ELISA and immunochemistry. After exposure to 100% O2 for 62 hr, survival was greater in rats injected with the catalase and/or SOD Ad vectors than in control rats. Ischemia-reperfusion injury was evaluated in the isolated perfused lung model. Overexpression of SOD worsened ischemia-reperfusion injury. Interestingly, concomitant overexpression of catalase prevented this adverse effect, but did not protect against ischemia-reperfusion injury. We conclude that Ad-mediated transfer to lungs of both catalase and SOD cDNAs protects from pulmonary O2 toxicity. Absence of protection against ischemia-reperfusion using intratracheal Ad injections may be related to the lack of endothelial protection, despite epithelial expression of catalase and SOD.

Original languageEnglish
Pages (from-to)1487-1496
Number of pages10
JournalHuman Gene Therapy
Volume9
Issue number10
DOIs
Publication statusPublished - 1 Jul 1998
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this