title: 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).
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. jykim@bu.edu
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Kim
authors.forename: Sudha
authors.initials: S
authors.lastname: Natarajan
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Vaickus
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Bouchard
authors.forename: Dominic
authors.initials: D
authors.lastname: Beal
authors.forename: William W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000403:Airway Resistance / Q000502:physiology; D000485:Allergens / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000139:chemically induced* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000139:chemically induced; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019743:Chemokines, CXC / Q000378:metabolism* / Q000502:physiology; D004391:Dust; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D000485:Allergens; D000911:Antibodies, Monoclonal; D019743:Chemokines, CXC; D004391:Dust; D052638:Particulate Matter; D001335:Vehicle Emissions