Interference of a short‐term exposure to nitrogen dioxide with allergic airways responses to allergenic challenges in BALB/c mice

Abstract

Nitrogen dioxide (NO(2)) is a common indoor and outdoor air pollutant whose role in the induction of asthma is unclear. We investigated the effects of NO(2) on the development of asthma-like responses to allergenic challenge in BALB/c mice. Ovalbumin (OVA)-immunized mice were intranasally challenged with OVA or saline solution just before starting a 3 h exposure to 5 or 20 ppm NO(2) or air. Twenty parts per million of NO(2) induced a significant increase of bronchopulmonary hyperreactivity in OVA-challenged mice and of permeability according to the fibronectin content of the bronchoalveolar lavage fluid (BALF) 24 h after exposure, as compared with air or 5 ppm NO(2). Eosinophilia (cell counts in the BALF and eosinophil peroxidase of lung tissue) was detected at 24 and 72 h with similar levels for air and 20 ppm NO(2), whereas a marked reduction was unexpectedly observed for 5 ppm NO(2). At 24 h, interleukin-5 in the BALF was markedly reduced at 5 ppm compared with 20 ppm NO(2) and was also more intense for 20 ppm NO(2) than for the air group. In contrast to specific IgG1 titers, anti-OVA IgE titers and interleukin-4 in the BALF were not affected by NO(2) exposure. Irrespective of the concentration of NO(2), OVA-challenged mice did not develop late mucosal metaplasia compared with those exposed to OVA-air. These results indicate that a short exposure to NO(2) can exacerbate or inhibit some features of the development of allergic disease in mice and may depend on the concentration of pollutant.

Nitrogen dioxide enhances allergic airway inflammation and hyperresponsiveness in the mouse

“…Although the dose of NO 2 administered to our mice was higher than those used in a number of previous studies (16,22,23,40) and are higher than the concentrations seen in ambient air, the actual concentrations of NO 2 that reach the lung tissue are likely to be far lower than 25 ppm, given the high reactivity of NO 2 toward airway surface lining components. Consequently, the patterns of tyrosine nitration observed within the lung tissue in situ using the current NO 2 exposure regimen were not substantially different from air controls (data not shown).…”

“…These discrepancies can be explained by differences in the time frame of exposure to NO 2 relative to the OVA challenge, the concentration and/or the duration of NO 2 inhalation, and the genetic backgrounds of mice investigated. For example, using allergen-sensitized BALB/c mice exposed to 20 ppm NO 2 immediately before an intranasal challenge with allergen, Proust et al (40) reported enhanced AHR and lung permeability 24 h after exposure, despite a lack of alterations in eosinophil numbers in the BALF at 24 or 72 h after challenge and a reduction of late mucosal metaplasia compared with mice sensitized and challenged with allergen (OVA) alone. This group also reported that 5 ppm NO 2 caused a reduction in many of the measured features of allergic airway disease (40).…”

“…For example, using allergen-sensitized BALB/c mice exposed to 20 ppm NO 2 immediately before an intranasal challenge with allergen, Proust et al (40) reported enhanced AHR and lung permeability 24 h after exposure, despite a lack of alterations in eosinophil numbers in the BALF at 24 or 72 h after challenge and a reduction of late mucosal metaplasia compared with mice sensitized and challenged with allergen (OVA) alone. This group also reported that 5 ppm NO 2 caused a reduction in many of the measured features of allergic airway disease (40). Using allergen-sensitized C57BL/6 mice exposed to 0.7 or 5 ppm NO 2 , Hubbard et al (22) also demonstrated reductions in eosinophil numbers in the BALF compared with air-exposed mice in response to subsequent challenge with allergen.…”

“…To date, a limited number of studies using mice have demonstrated contradictory effects (22,23,40), possibly due to the use of different mouse strains, different doses of NO 2 , and different timing of the NO 2 administration. The goal of the present study was to document the effects of NO 2 exposure on the mouse lung and to determine whether 5 or 25 ppm NO 2 exposure exacerbated allergic airways disease or promoted chronic alterations in the allergic inflamed lung.…”

Macrophage activation by gastric fluid suggests MMP involvement in aspiration-induced lung disease

“…The production of MMP-12 was stimulated by IL-1b and TNF-a, and was found to promote cell migration (Xie et al 2005). In addition, deficiency in MMP-9 in a mouse model was found to be associated with decreased lung or alveolar injury (Lanone et al 2002;Proust et al 2002;Zuo et al 2002). Further, increased MMP-2 and -14 activity was found to be associated with asthmatic airway smooth muscle (Henderson et al 2007).…”