Diesel Exhaust Particulates Exacerbate Asthma-Like Inflammation by Increasing CXC Chemokines

Abstract

Particulate matter heavily pollutes the urban atmosphere, and several studies show a link between increased ambient particulate air pollution and exacerbation of pre-existing pulmonary diseases, including asthma. We investigated how diesel exhaust particulates (DEPs) aggravate asthma-like pulmonary inflammation in a mouse model of asthma induced by a house dust extract (HDE) containing cockroach allergens and endotoxin. BALB/c mice were exposed to three pulmonary challenges via hypopharyngeal administration of an HDE collected from the home of an asthmatic child. One hour before each pulmonary challenge, mice were exposed to DEP or PBS. Pulmonary inflammation was assessed by histological features, oxidative stress, respiratory physiological features, inflammatory cell recruitment, and local CXC chemokine production. To prove the role of CXC chemokines in the augmented inflammation, CXC chemokine-specific antibodies were delivered to the lungs before DEP exposure. DEP exacerbated HDE-induced airway inflammation, with increased airway mucus production, oxidative stress, inflammatory cell infiltration, bronchoalveolar lavage concentrations of CXC chemokines, and airway hyperreactivity. Neutralization of airway keratinocyte-derived chemokine and macrophage inflammatory protein-2 significantly improves the respiratory function in addition to decreasing the infiltration of neutrophils and eosinophils. Blocking the chemokines also decreased airway mucus production. These results demonstrate that DEP exacerbates airway inflammation induced by allergen through increased pulmonary expression of the CXC chemokines (keratinocyte-derived chemokine and macrophage inflammatory protein-2).

A mouse model links asthma susceptibility to prenatal exposure to diesel exhaust

“…The DEP dose of 50 μg is commonly used in mouse models, including those by Auten at al. and Fedulov et al 13, 14, and 16 . We considered using exposure to titanium dioxide or carbon black particles because they were used in some studies as “control” particles.…”

Genetic variation influences immune responses in sensitive rats following exposure to TiO2 nanoparticles

“…Several studies have been published on the effects of ambient particulate exposure on allergic airway disease (Arantes-Costa et al, 2008;Kim et al, 2011) and, more recently, on the impact of ENMs on rats with allergic diseases (Hussain et al, 2011;Koike et al, 2008;Nygaard et al, 2009;Rossi et al, 2010a,b). The results from these studies vary, probably as a consequence of using different protocols, differing in choice of strains and sensitization schedule.…”

Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

“…115 Furthermore, diesel exhaust particulate exposure increased innate airway inflammation, mucus secretion and AHR via a KC/CXCL1 and macrophage inflammatory protein (MIP)-2/CXCL2-dependent mechanism, in a cockroach antigen model. 116 These studies indicate that lung exposure to components of environmental pollution can also modulate the local inflammatory responses by potentiating type-2 inflammation or increasing innate inflammatory responses, which exacerbate preexisting allergic inflammation.…”