Nitration of Protein Without Allergenic Potential Triggers Modulation of Antioxidant Response in Type II Pneumocytes

Abstract

Inhalation of nitrogen and reactive oxygen species (ROS) is known to induce lung inflammation, which is prevented by enzymatic and nonenzymatic antioxidant systems. These agents form nitrated allergens that were shown to enhance allergenicity. The aim of this study was to examine the influence of nitrated proteins on inflammation and antioxidant status of the lung. Ovalbumin (OVA) in nitrated form (nOVA) was intraperitoneally (ip) injected in mice for sensitization and in nitrated or unmodified form for challenge to induce allergic bronchial inflammation. To study the allergen potential of unrelated protein and verify cross-reactivity, nitrated and unmodified keyhole limpet hemocyanin (nKLH, KLH) was used for challenge. Challenge with OVA or nOVA reduced lung function and increased eosinophilia and protein content in bronchoalveolar lavage fluid (BALF). Challenge with nitrated or native OVA or KLH elevated glutathione (GSH) ratio in type II pneumocytes. Reduced mRNA expression of glutathione peroxidase (GPX) 3, glutathione reductase (GR), superoxide dismutase (SOD) 2, and catalase (CAT) was most prominent after challenge with nitrated OVA and nitrated KLH, respectively. Challenge with nOVA enhanced SOD1 mRNA reduction. Immunostaining of GPX 3 and SOD2 increased after challenge with OVA or nOVA, while reactivity of GR and reactivity of SOD2 were reduced after challenge with KLH or nKLH. SOD1 immunostaining was diminished after challenge with nonnitrated OVA or KLH. CAT immunoreaction was similar in all groups. Nitrated proteins without allergenic potential triggered mRNA reduction of antioxidants in type II cells after sensitization with a nitrated allergen but did not induce bronchial inflammation.

Air Pollution and Climate Change Effects on Allergies in the Anthropocene: Abundance, Interaction, and Modification of Allergens and Adjuvants

“…Moreover, increased proteolytic stability, up-regulation of CCL17 (Th2-associated chemokine secreted by dendritic cells, DC), and alterations of T cell proliferation and stimulatory capacities have been observed for nitrated Bet v 1 . Nitrated proteins also have been observed to modulate the antioxidant levels in murine pneumocytes . In a recent study, in vivo fumigation of ragweed pollen with NO 2 resulted in an altered proteomic pattern including nitrosylation products and the treated pollen showed higher IgE recognition in immunoblots .…”

“…306 Nitrated proteins also have been observed to modulate the antioxidant levels in murine pneumocytes. 352 In a recent study, in vivo fumigation of ragweed pollen with NO 2 resulted in an altered proteomic pattern including nitrosylation products and the treated pollen showed higher IgE recognition in immunoblots. 239 Enhanced allergenic potential was also observed for Betula pendula , Ostrya carpinifolia , and Carpinus betulus pollen after NO 2 exposure (Table S1).…”

Protein Cross-Linking and Oligomerization through Dityrosine Formation upon Exposure to Ozone

“…The prevalence of allergies is increasing worldwide, , and air pollution has been identified as one of the factors potentially responsible for this trend, but the underlying chemical mechanisms remain unclear . Air pollutants can directly affect the immune system, e.g., by inducing inflammation or oxidative stress, − and reactive trace gases like ozone (O 3 ) and nitrogen dioxide (NO 2 ) can induce post-translational modifications altering the immunogenicity of proteins. − …”