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Updated: May 11, 2026
Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models
Published on: October 22, 2012
Preservation of complement-induced lung injury in mice with deficiency of NADPH oxidase
H Kubo1, D Morgenstern, W M Quinian
1Herman B. Wells Center for Pediatric Research, Indiana University Medical Center, Indianapolis 46202, USA.
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-1beta 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.
Insights
Mice lacking NADPH oxidase (X-CGD mice) still developed lung injury from cobra venom factor, indicating alternative injury pathways exist. Neutrophils were essential, but catalase protection was lost in X-CGD mice.
Area of Science:
- Immunology
- Pathology
- Molecular Biology
Background:
- Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by impaired function of NADPH oxidase.
- NADPH oxidase plays a critical role in neutrophil-mediated host defense and inflammatory responses.
- Cobra venom factor (CVF) induces neutrophil-dependent lung injury in wild-type mice, sensitive to catalase.
Purpose of the Study:
- To investigate the role of NADPH oxidase in CVF-induced lung injury.
- To explore alternative pathways of lung injury in the absence of functional NADPH oxidase.
- To compare the mechanisms of CVF-induced lung injury in X-CGD mice and wild-type mice.
Main Methods:
- Generation of X-linked chronic granulomatous disease (X-CGD) mice by gene mutation.
- Intravenous injection of purified cobra venom factor (CVF) in X-CGD and wild-type mice.
- Measurement of extravascular albumin accumulation as an indicator of lung injury.
- Assessment of the protective effects of catalase, N(G)-methyl-L-arginine, and allopurinol.
- Analysis of lung mRNA expression for inducible nitric oxide synthase and IL-1beta.
Main Results:
- X-CGD mice exhibited similar CVF-induced lung injury as wild-type mice, measured by albumin accumulation.
- Neutrophils were required for injury development in both X-CGD and wild-type mice.
- Catalase lost its protective effect in X-CGD mice, while N(G)-methyl-L-arginine became protective.
- Allopurinol provided protection in both mouse models.
- CVF-inducible mRNA levels for iNOS and IL-1beta were comparable between X-CGD and wild-type mice.
Conclusions:
- CVF-induced lung injury in mice lacking NADPH oxidase function occurs via pathways independent of direct oxygen radical production by this enzyme.
- Neutrophils are central to the injury, but their activation or effector mechanisms differ in the absence of NADPH oxidase.
- Nitric oxide pathways may play a more significant role in CVF-induced lung injury in X-CGD mice.
- These findings highlight the complexity of inflammatory responses and identify alternative mechanisms contributing to tissue injury.
