BALT development and augmentation of hyperoxic lung injury in mice deficient in NQO1 and NQO2

Amitava Das, Labanyamoy Kole, Lihua Wang, Roberto Barrios, Bhagavatula Moorthy, Anil K. Jaiswal

Research output: Contribution to journalArticle

28 Scopus citations

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 TNFα, IL-6, and IL-1β 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.

Original languageEnglish (US)
Pages (from-to)1843-1856
Number of pages14
JournalFree Radical Biology and Medicine
Volume40
Issue number10
DOIs
StatePublished - May 15 2006

Keywords

  • BALT
  • Double knockout
  • Free radicals
  • Lung inflammation
  • NQO1
  • NQO2

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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