Preservation of complement-induced lung injury in mice with deficiency of NADPH oxidase

Hiroshi Kubo, David Morgenstern, William M. Quintan, Peter A. Ward, Mary C. Dinauer, Claire M. Doerschuk

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)

Abstract

Mice with chronic granulomatous disease (X-CGD mice) generated by mutating the X-linked gene for a subunit of NADPH oxidase have been analyzed for their ability to respond to intravenous injection of purified cobra venom factor (CVF). This agent in wild-type mice produces a neutrophil-dependent and catalase-sensitive form of lung injury. Lung injury was evaluated by measuring the accumulation of extravascular albumin. Quite unexpectedly, the lungs of X-CGD mice showed no difference in the increased accumulation of extravascular albumin after injection of CVF when compared to wild-type mice. In both X-CGD and wild-type mice, full development of injury required neutrophils. While catalase was highly protective in wild-type mice, its protective effects were completely lost in the X-CGD mice. Furthermore, a competitive antagonist of L-arginine, N(G)-methyl-L-arginine, was protective in X-CGD mice but not in wild-type mice. Allopurinol was protective in both types of mice. Both the basal and the CVF-inducible lung mRNA for inducible nitric oxide synthase and IL-1β was similar in X-CGD and wild-type mice. These data indicate that oxygen radical production and lung injury in response to injection of CVF occurs through alternative pathways in mice with genetic deletion of NADPH oxidase.

Original languageEnglish
Pages (from-to)2680-2684
Number of pages5
JournalJournal of Clinical Investigation
Volume97
Issue number11
DOIs
Publication statusPublished - 1996 Jun 1

Keywords

  • chronic granulomatous disease
  • hydroxyl radical
  • lung injury
  • neutrophils
  • nitric oxide

ASJC Scopus subject areas

  • Medicine(all)

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