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.