title: Diesel exhaust particles exert acute effects on airway inflammation and function in murine allergen provocation models.
abstract: BACKGROUND
  Epidemiologic studies show that sudden surges in ambient particulate matter (PM) levels can trigger acute asthma exacerbations. Although diesel exhaust particles (DEPs) act as an adjuvant for allergic sensitization, this is a delayed response and does not explain acute PM effects on airway hyperreactivity (AHR).
  
  
  OBJECTIVE
  Our aim was to determine the acute effects of DEPs on AHR using a mouse model.
  
  
  METHODS
  Three protocols were developed, 2 of which require OVA sensitization, whereas the third was OVA independent. In the mild sensitization protocol BALB/c mice receive intraperitoneal OVA without alum and are then challenged with aerosolized OVA with or without DEPs. In the postchallenge model DEPs are delivered after OVA challenge to animals sensitized by intraperitoneal OVA plus alum. In the third protocol nebulizer DEPs were also delivered to IL-5-overexpressing mice that exhibit constitutive airway inflammation. Animals were subjected to whole-body plethysmography (WBP) and then killed for performance of bronchoalveolar lavage, histology, and serology.
  
  
  RESULTS
  DEP delivery concomitant with OVA challenge or after the induction of airway inflammation with this allergen induced increased AHR in models 1 and 2, respectively. Although these animals showed DEP-induced inflammation and mucus production in the intermediary airways, there was no effect on OVA-specific IgE or T(H)2 cytokine production. In the IL-5 transgenic mice it was possible to induce similar effects with DEPs in the absence of an allergen.
  
  
  CONCLUSIONS
  We demonstrate that DEPs induced AHR independent of their adjuvant effects, suggesting the use of these models to study the mechanism or mechanisms of acute asthma exacerbation by means of PM.
authors: Department of Medicine, UCLA School of Medicine, University of California, Los Angeles, USA.
authors: Minqi
authors: M
authors: Hao
authors: Stephania
authors: S
authors: Comier
authors: Meiying
authors: M
authors: Wang
authors: James J
authors: JJ
authors: Lee
authors: Andre
authors: A
authors: Nel
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D005260:Female; D007114:Immunization; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic / Q000235:genetics; D009077:Mucins / Q000378:metabolism; D012123:Pulmonary Ventilation; D012140:Respiratory Tract Diseases / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001335:Vehicle Emissions / Q000009:adverse effects*
chemical_list: D000485:Allergens; D015848:Interleukin-5; D009077:Mucins; D001335:Vehicle Emissions