BALB/c and C57BL/6 mice differ in oxidant and antioxidant responses in innate and adaptive immune cells in an asthma model induced by cockroach allergens.

• Neutrophilic airway inflammation was higher in the BALB/c strain than in the C57 strain in a murine model of cockroach-induced asthma (CA). • Pulmonary oxidative stress was higher in the BALB/c strain than in the C57 strain in CA. • Pulmonary antioxidant levels were lower in the BALB/c strain than in the C57 strain in CA. • There was significant interaction between allergen exposure and antioxidant responses between BALB/c strain and C57 strain. Asthma is a complex and heterogenous disease affected by a multitude of factors. Several phenotypes of asthma exist which are influenced by various molecular mechanisms that include presence of antioxidant and oxidant enzymes in different immune cells such as dendritic cells (DCs), alveolar macrophages (AMs), neutrophils, and T cells. Close interaction between epithelial cells and dendritic cells initiates complex pathogenesis of asthma followed by involvement of other innate and adaptive immune cells. In chronic phase of the disease, these immune cells support each other in amplification of airway inflammation where oxidant-antioxidant balance is known to be an important contributing factor. Genetic variability in antioxidant response may influence the development of airway inflammation, however it has not been studied in mice yet. The two most studied mice strains, i.e. BALB/c and C57BL/6 are reported to have dissimilar airway responses to the same allergens due to their genetic makeup. In this investigation, we explored whether these strains had any differences in pulmonary oxidant-antioxidant system (Nrf2, SOD2, iNOS, HO-1, nitrotyrosine) in different immune cells (DCs, AMs, neutrophils, T cells), airway inflammation (presence of eosinophils and/or neutrophils) and mucus production in response to repeated cockroach allergen extract (CE) mouse model of asthma. Our data show that C57BL/6 mice had better induction of antioxidant system than BALB/c mice. Consequently, iNOS/nitrotyrosine levels were much exaggerated in BALB/c than C57BL/6 mice. As a result, BALB/c mice developed mixed granulocytic airway inflammation, whereas C57BL/6 developed mostly eosinophilic airway inflammation. Our data suggest that an exaggerated oxidant generation along with a weak antioxidant induction in response to a natural allergen on a susceptible genetic background may determine development of severe asthma phenotype such as mixed granulocyte inflammation. [ABSTRACT FROM AUTHOR]