Effects of ultrafine particles-induced oxidative stress on Clara cells in allergic lung inflammation

Abstract

BackgroundClara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against oxidative stress and inflammation. The purpose of the study was to investigate the role of elemental carbon ultrafine particles (EC-UFP)-induced oxidative stress on Clara cells and CC16 in a mouse model of allergic lung inflammation.MethodsOvalbumin (OVA)-sensitized mice were exposed to EC-UFP (507 μg/m3 for 24 h) or filtered air immediately prior to allergen challenge and systemically treated with N-acetylcysteine (NAC) or vehicle prior and during EC-UFP inhalation. CC16 was measured up to one week after allergen challenge in bronchoalveolar lavage fluid (BALF) and in serum. The relative expression of CC16 and TNF-α mRNA were measured in lung homogenates. A morphometrical analysis of mucus hypersecretion and electron microscopy served to investigate goblet cell metaplasia and Clara cell morphological alterations.ResultsIn non sensitized mice EC-UFP inhalation caused alterations in CC16 concentration, both at protein and mRNA level, and induced Clara cell hyperplasia. In sensitized mice, inhalation of EC-UFP prior to OVA challenge caused most significant alterations of BALF and serum CC16 concentration, BALF total protein and TNF-α relative expression compared to relevant controls; their Clara cells displayed the strongest morphological alterations and strongest goblet cell metaplasia occurred in the small airways. NAC strongly reduced both functional and morphological alterations of Clara cells.ConclusionOur findings demonstrate that oxidative stress plays an important role in EC-UFP-induced augmentation of functional and morphological alterations of Clara cells in allergic lung inflammation.

A work group report on ultrafine particles (American Academy of Allergy, Asthma & Immunology): Why ambient ultrafine and engineered nanoparticles should receive special attention for possible adverse health outcomes in human subjects

“…113 Exposure of sensitized mice to EC-UFP prior to OVA challenge also led to the goblet cell metaplasia of Clara cells and overproduction of mucus and Clara cell protein. 114 These changes as well as the adjuvant activity of EC-UFP could be suppressed by antioxidant N-acetyl cysteine. 113, 114 In addition to their capability of up-regulating pro-inflammatory cytokines and chemokines through oxidative stress, UFP also alter the balance between pro- and anti-inflammatory lipid mediators.…”

“…114 These changes as well as the adjuvant activity of EC-UFP could be suppressed by antioxidant N-acetyl cysteine. 113, 114 In addition to their capability of up-regulating pro-inflammatory cytokines and chemokines through oxidative stress, UFP also alter the balance between pro- and anti-inflammatory lipid mediators. Exposure of OVA-sensitized mice to ultrafine carbon particles before OVA challenge enhanced allergic inflammation and lipid peroxidation in the lung and skewed lipid mediator balance towards a pro-inflammatory response with a significant increase of leukotriene B4.…”

Effects of nitrogen-doped multi-walled carbon nanotubes compared to pristine multi-walled carbon nanotubes on human small airway epithelial cells

“…MWCNT-7 have been shown to induce inflammation and fibrosis in vivo at occupationally relevant doses in mice and rats (Mercer et al, 2010, 2013; Porter et al, 2010, 2013). At an inhalation exposure of 5 mg/m 3 , MWCNT-7 were capable of bypassing the defenses of the mouse lung due to their small size, with approximately 84% of the MWCNT-7 found in the alveolar region one day post-exposure (Mercer et al, 2011).…”

Die Achse Umwelt‐Erreger‐Wirt bei übertragbaren und nicht übertragbaren Krankheiten: Jüngste Fortschritte in der experimentellen und klinischen Forschung

“…Wir hatten bereits gezeigt, dass ultrafeine Partikel, wie sie in Diesel-Abgasen vorkommen, allergisches Asthma in einem Mausmodell verstärken [18,19]. Insgesamt gibt es eine solide Datenbasis dafür, dass industrielle und verkehrsbedingte Luftschadstoffe die Inzidenz atopischer Erkrankungen erhöhen und in ihrer Ausprägung verschärfen (Review in [20]).…”