Exposure of humans to particulate air pollution has been correlated with the incidence and aggravation of allergic airway diseases. In predisposed individuals, inhalation of environmental particles can lead to an exacerbation of immune responses. Previous studies demonstrated a beneficial effect of the compatible solute ectoine on lung inflammation in rats exposed to carbon nanoparticles (CNP) as a model of environmental particle exposure. In the current study we investigated the effect of such a treatment on airway inflammation in a mouse allergy model. Ectoine in nonsensitized animals significantly reduced the neutrophilic lung inflammation after CNP exposure. This effect was accompanied by a reduction of inflammatory factors in the bronchoalveolar lavage. Reduced IL-6 levels in the serum also indicate the effects of ectoine on systemic inflammation. In sensitized animals, an aggravation of the immune response was observed when animals were exposed to CNP prior to antigen provocation. The coadministration of ectoine together with the particles significantly reduced this exacerbation. The data indicate the role of neutrophilic lung inflammation in the exacerbation of allergic airway responses. Moreover, the data suggest to use ectoine as a preventive treatment to avoid the exacerbation of allergic airway responses induced by environmental air pollution. 1. Introduction The exposure of humans to particulate air pollution has been correlated with the incidence of atopic allergies [1]. In particular, traffic-related air pollution is strongly linked to allergic diseases including asthmatic bronchitis [2]. It is hypothesized that an adjuvant effect of inhaled particles may influence either the process of sensitization or the immune response, at the level of the disease outcome [3]. In asthma patients, such adverse effects of particulate air pollution can be observed as an acute exacerbation of allergic lung inflammation [4–6]. Current research is focusing on the molecular mechanisms by which such a toxic potential of environmental particles is mediated. As one common denominator of particle-induced adverse health effects, oxidative stress in the airways has been identified [7]. Reactive oxygen species may be triggered by the intrinsic oxidative potential of inhaled particulate matter which depends on chemical properties like elemental composition and surface charges. But also via indirect cell mediated pathways oxidative stress is generated in the airways. Upon cell contact, in particular ultrafine or nano-sized particles may interact with cellular
References
[1]
H. S. Koren, “Environmental risk factors in atopic asthma,” International Archives of Allergy and Immunology, vol. 113, no. 1–3, pp. 65–68, 1997.
[2]
V. Morgenstern, A. Zutavern, J. Cyrys et al., “Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children,” The American Journal of Respiratory and Critical Care Medicine, vol. 177, no. 12, pp. 1331–1337, 2008.
[3]
S. H. Gavett and H. S. Koren, “The role of particulate matter in exacerbation of atopic asthma,” International Archives of Allergy and Immunology, vol. 124, no. 1–3, pp. 109–112, 2001.
[4]
E. Samoli, P. T. Nastos, A. G. Paliatsos, K. Katsouyanni, and K. N. Priftis, “Acute effects of air pollution on pediatric asthma exacerbation: evidence of association and effect modification,” Environmental Research, vol. 111, no. 3, pp. 418–424, 2011.
[5]
K. Evans, J. S. Halterman, P. K. Hopke, M. Fagnano, and D. Q. Rich, “Increased utrafine particles and carbon monoxide concentrations are associated with asthma exacerbation among urban children,” Environmental Research, vol. 129, pp. 11–19, 2014.
[6]
W. Lin, W. Huang, T. Zhu et al., “Acute respiratory inflammation in children and black carbon in ambient air before and during the 2008 Beijing Olympics,” Environmental Health Perspectives, vol. 119, no. 10, pp. 1507–1512, 2011.
[7]
M. A. Riedl and A. E. Nel, “Importance of oxidative stress in the pathogenesis and treatment of asthma,” Current Opinion in Allergy and Clinical Immunology, vol. 8, no. 1, pp. 49–56, 2008.
[8]
K. Unfried, C. Albrecht, L. Klotz, A. von Mikecz, S. Grether-Beck, and R. P. F. Schins, “Cellular responses to nanoparticles: target structures and mechanisms,” Nanotoxicology, vol. 1, no. 1, pp. 52–71, 2007.
[9]
P. J. Barnes, “Reactive oxygen species and airway inflammation,” Free Radical Biology and Medicine, vol. 9, no. 3, pp. 235–243, 1990.
[10]
F. Alessandrini, H. Schulz, S. Takenaka et al., “Effects of ultrafine carbon particle inhalation on allergic inflammation of the lung,” Journal of Allergy and Clinical Immunology, vol. 117, no. 4, pp. 824–830, 2006.
[11]
F. Alessandrini, I. Beck-Speier, D. Krappmann et al., “Role of oxidative stress in ultrafine particle-induced exacerbation of allergic lung inflammation,” The American Journal of Respiratory and Critical Care Medicine, vol. 179, no. 11, pp. 984–991, 2009.
[12]
U. Sydlik, I. Gallitz, C. Albrecht, J. Abel, J. Krutmann, and K. Unfried, “The compatible solute ectoine protects against nanoparticle-induced neutrophilic lung inflammation,” The American Journal of Respiratory and Critical Care Medicine, vol. 180, no. 1, pp. 29–35, 2009.
[13]
H. Peuschel, U. Sydlik, S. Grether-Beck et al., “Carbon nanoparticles induce ceramide- and lipid raft-dependent signalling in lung epithelial cells: a target for a preventive strategy against environmentally-induced lung inflammation,” Particle and Fibre Toxicology, vol. 9, article 48, 2012.
[14]
U. Sydlik, H. Peuschel, A. Paunel-G？rgülü et al., “Recovery of neutrophil apoptosis by ectoine: a new strategy against lung inflammation,” European Respiratory Journal, vol. 41, no. 2, pp. 433–442, 2013.
[15]
M. Rincon and C. G. Irvin, “Role of IL-6 in asthma and other inflammatory pulmonary diseases,” International Journal of Biological Sciences, vol. 8, no. 9, pp. 1281–1290, 2012.
[16]
H. Peuschel, U. Sydlik, J. Haendeler et al., “C-Src-mediated activation of Erk1/2 is a reaction of epithelial cells to carbon nanoparticle treatment and may be a target for a molecular preventive strategy,” Biological Chemistry, vol. 391, no. 11, pp. 1327–1332, 2010.
[17]
I. Beck-Speier, E. Karg, H. Behrendt, T. Stoeger, and F. Alessandrini, “Ultrafine particles affect the balance of endogenous pro- and anti-inflammatory lipid mediators in the lung: in-vitro and in-vivo studies,” Particle and Fibre Toxicology, vol. 9, article 27, 2012.
[18]
C. L. Ordo？ez, T. E. Shaughnessy, M. A. Matthay, and J. V. Fahy, “Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: clinical and biologic significance,” The American Journal of Respiratory and Critical Care Medicine, vol. 161, no. 4, pp. 1185–1190, 2000.
[19]
S. E. Wenzel, “Asthma: defining of the persistent adult phenotypes,” The Lancet, vol. 368, no. 9537, pp. 804–813, 2006.
