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Updated: Aug 8, 2026
Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models
Published on: October 22, 2012
BALT development and augmentation of hyperoxic lung injury in mice deficient in NQO1 and NQO2
Amitava Das1, Labanyamoy Kole, Lihua Wang
1Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Abstract:
NAD(P)H/NRH:quinone oxidoreductases (NQO1 and NQO2) protect against oxidative stress and neoplasia. Cross-breeding of NQO1-/- with NQO2-/- mice generated double-knockout (DKO) mice. DKO mice were born normal yet showed myelogenous hyperplasia as observed in single-knockout mice. DKO mice also showed bronchial-associated lymphoid tissue (BALT) that increased in number and size with age. BALT was absent in wild-type and single-knockout mice. Further analysis demonstrated infiltration of neutrophils and macrophages in BALT and significant increases in the serum cytokines TNFalpha, IL-6, and IL-1beta and increased expression of iNOS and higher nitric oxide in lung macrophages. The development of BALT in DKO mice presumably led to the release of cytokines and higher lung macrophage activation, because histologically spleen, thymus, and blood cultures and urine analysis showed absence of infection. Additionally, the DKO mice upon exposure to hyperoxia demonstrated severe intra-alveolar edema and perivascular inflammation and massive infiltration with neutrophils, compared with wild-type mice. These results suggest that NQO1 and NQO2 combined protect mice against lung inflammation, BALT, and hyperoxic lung injury.
Insights
The study reveals that NAD(P)H:quinone oxidoreductase 1 (NQO1) and NQO2 enzymes are crucial for preventing lung inflammation and injury. Double-knockout mice lacking both NQO1 and NQO2 developed significant lung issues, highlighting their protective roles.
Area of Science:
- Biochemistry
- Immunology
- Toxicology
Background:
- NAD(P)H:quinone oxidoreductases (NQO1 and NQO2) are key enzymes involved in cellular protection against oxidative stress and the development of neoplasia.
- While NQO1 and NQO2 individually contribute to cellular defense, their combined role in lung health and inflammatory responses remains incompletely understood.
Purpose of the Study:
- To investigate the combined protective functions of NQO1 and NQO2 in the context of lung inflammation and injury.
- To determine the impact of simultaneous NQO1 and NQO2 deficiency on lung tissue, immune cell infiltration, and inflammatory markers.
Main Methods:
- Generation of double-knockout (DKO) mice lacking both Nqo1 and Nqo2 genes through cross-breeding.
- Histological analysis of lung tissue, including assessment of bronchial-associated lymphoid tissue (BALT) formation and immune cell infiltration (neutrophils, macrophages).
- Measurement of serum cytokine levels (TNF-alpha, IL-6, IL-1beta), iNOS expression, and nitric oxide production in lung macrophages.
- Evaluation of lung response to hyperoxia exposure in DKO and wild-type mice.
Main Results:
- DKO mice exhibited myelogenous hyperplasia and developed age-dependent bronchial-associated lymphoid tissue (BALT), which was absent in wild-type and single-knockout mice.
- BALT in DKO mice was characterized by neutrophil and macrophage infiltration, elevated serum cytokines (TNF-alpha, IL-6, IL-1beta), increased iNOS expression, and higher nitric oxide levels.
- DKO mice showed significantly exacerbated lung injury, including intra-alveolar edema, perivascular inflammation, and neutrophil infiltration upon hyperoxia exposure compared to wild-type controls.
Conclusions:
- Combined deficiency of NQO1 and NQO2 leads to spontaneous development of lung inflammation, BALT, and heightened susceptibility to hyperoxic lung injury.
- NQO1 and NQO2 play a critical, synergistic role in protecting the lungs against inflammatory processes and acute lung injury.
