Diesel exhaust particles exert acute effects on airway inflammation and function in murine allergen provocation models.
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.
Hao
Minqi
M
Department of Medicine, UCLA School of Medicine, University of California, Los Angeles, USA.
Comier
Stephania
S
Wang
Meiying
M
Lee
James J
JJ
Nel
Andre
A
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*
D000485:Allergens; D015848:Interleukin-5; D009077:Mucins; D001335:Vehicle Emissions