Nitrogen Dioxide Promotes Allergic Sensitization to Inhaled Antigen

Abstract

Allergen sensitization and allergic airway disease are likely to come about through the inhalation of Ag with immunostimulatory molecules. However, environmental pollutants, including nitrogen dioxide (NO2), may promote adaptive immune responses to innocuous Ags that are not by themselves immunostimulatory. We tested in C57BL/6 mice whether exposure to NO2, followed by inhalation of the innocuous protein Ag, OVA, would result in allergen sensitization and the subsequent development of allergic airway disease. Following challenge with aerosolized OVA alone, mice previously exposed via inhalation to NO2 and OVA developed eosinophilic inflammation and mucus cell metaplasia in the lungs, as well as OVA-specific IgE and IgG1, and Th2-type cytokine responses. One hour of exposure to 10 parts per million NO2 increased bronchoalveolar lavage fluid levels of total protein, lactate dehydrogenase activity, and heat shock protein 70; promoted the activation of NF-κB by airway epithelial cells; and stimulated the subsequent allergic response to Ag challenge. Furthermore, features of allergic airway disease were not induced in allergen-challenged TLR2−/− and MyD88−/− mice exposed to NO2 and aerosolized OVA during sensitization. These findings offer a mechanism whereby allergen sensitization and asthma may result under conditions of high ambient or endogenous NO2 levels.

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…Alberg et al (2011) were not able to detect an impact of NO 2 on allergy induced by ovalbumin, whereas diesel exhaust particles were shown to be a potent adjuvant. In contrast, Bevelander et al (2007) and Hodgkins et al (2010) did find a potentiating effect of NO 2 within the concentration range used by Alberg et al (2011) (5-25 ppm) when NO 2 exposure occurred immediately beforehand and ovalbumin exposure was by inhalation. Recent in vitro findings suggested that levels of SO 2 and NO 2 below current EU health based exposure standards can exacerbate pollen allergy on susceptible subjects (Sousa et al, 2012).…”

Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes

“…Overweight and obese children are more susceptible to indoor air pollutants, especially particulate matter and nitrogen dioxide, than are lean children (63). We have reported that in nonobese mouse models, nitrogen dioxide inhalation causes allergic asthma-like disease through NLRP3 and IL-1 signaling (64) and inherent asthma-like disease through activation of the transcription factor nuclear factor-kB (NF-kB) in the airway epithelium (65). Airway epithelial NF-kB activation increases methacholine responsiveness (in the absence of allergen exposure) by increasing the abundance of airway smooth muscle (66), increases lung type 2 innate lymphoid cells, and facilitates allergic antigen sensitization (67,68).…”

Interleukin-1 Receptor and Caspase-1 Are Required for the Th17 Response in Nitrogen Dioxide–Promoted Allergic Airway Disease

“…Exposure to NO 2 positively correlates with asthma severity, the risk of hospitalization, disease exacerbation, the risk of death, and the development of asthma in previously healthy children (8)(9)(10). We have reported that NO 2 exposure allergically sensitizes mice to ovalbumin (OVA; we define sensitization as the act or process of inducing an acquired allergy), inducing methacholine airway hyperresponsiveness (AHR), antigen-specific IgG1 and IgE, inflammatory leukocyte recruitment to the airway, and the production of Th2 cytokines and IL-17 during in vitro restimulation of CD4 1 T cells (11,12). Th17 cells comprise a distinct subset of T cell receptor (TCR)ab 1 CD4 1 T cells that are characterized by the production of IL-17A, IL-17F, and IL-22 and the transcription factor retinoic acid receptor-related orphan receptor (ROR)gt.…”

“…NO 2 exposure rapidly leads to NF-kB activation in airway epithelia, and later, the up-regulation of Saa3 and the production of SAA3 from airway epithelia (6,11,28). SAA is a candidate downstream mediator of NO 2 -promoted allergic sensitization (6,28,49).…”