Journal ArticleDOI
Diesel exhaust particle exposure increases severity of allergic asthma in young mice
Thomas H. Acciani,Thomas H. Acciani,Eric B. Brandt,Eric B. Brandt,G.K. Khurana Hershey,G.K. Khurana Hershey,T. D. Le Cras,T. D. Le Cras +7 more
TLDR
Epidemiologic studies have reported an association between diesel exhaust particle exposure, allergic sensitization, and childhood wheezing, although the mechanisms remain unclear.Abstract:
SummaryBackground
Epidemiologic studies have reported an association between diesel exhaust particle (DEP) exposure, allergic sensitization, and childhood wheezing, although the mechanisms remain unclear. While DEP is known to augment allergic responses in adult animal models, its effects on sensitization and asthma severity in young animals is unknown.
Objective
To examine the impact of different doses of DEP and allergen co-exposure on allergic sensitization and asthma characteristics in young mice, and whether Th17 as well as Th2 responses are induced.
Methods
Lungs of 3-week-old wild-type Balb/c mice were exposed by pharyngeal aspiration nine times over 3 weeks to DEP at 1.2 or 6.0 mg/kg body weight, house dust mite (HDM) at 0.8, 1.2 or 6.0 mg/kg of DEP in combination with HDM, or the same volume (50 μL) of 0.9% sterile saline.
Results
In young mice, exposure to 1.2 mg/kg of DEP caused no detectable lung inflammation, but 6.0 mg/kg of DEP induced neutrophilic influx. Compared to HDM or DEP alone, mice exposed to either dose of DEP together with HDM demonstrated increased allergen-specific IgE, lung inflammation, airway hyperreactivity, goblet cell metaplasia, Th2/Th17 cytokines, dendritic cells, activated T cells, effector T cells, and IL-17pos and IL-13pos/IL-17Apos T effector cells.
Conclusions and Clinical Relevance
In young mice, co-exposure to DEP and HDM together exacerbated allergic sensitization and induced key characteristics of more severe asthma, including IL-17A, IL-17pos and IL-13pos/IL-17Apos T effector cells. While exposure to 1.2 mg/kg DEP alone caused no detectable changes, it did exacerbate allergic sensitization and asthma characteristics to a similar degree as a five-fold higher dose of DEP. This study demonstrates that exposure to DEP, even at a dose that alone causes no inflammation, exacerbates allergic asthma in young animals and suggests the importance of preventive measures to reduce the exposure of children to traffic related air pollution.read more
Citations
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Outdoor air pollution and asthma
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Lung Homeostasis: Influence of Age, Microbes, and the Immune System.
TL;DR: It is proposed that host interactions with microbes are critical for establishing the immune landscape of the lungs and in the setting of the threshold for immune responses that maintains the balance between tolerance and chronic inflammation in the lung.
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A Comparison of the Health Effects of Ambient Particulate Matter Air Pollution from Five Emission Sources.
TL;DR: The evidence to date does not indicate a clear ‘hierarchy’ of harmfulness for PM from different emission sources, and further investigations of the health effects of source-specific PM with more advanced approaches to exposure modeling, measurement, and statistics are required before changing the current public health protection approach of minimising exposure to total PM mass.
Journal ArticleDOI
Exposure to allergen and diesel exhaust particles potentiates secondary allergen-specific memory responses, promoting asthma susceptibility
Eric B. Brandt,Jocelyn M. Biagini Myers,Thomas H. Acciani,Patrick Ryan,Umasundari Sivaprasad,Brandy P. Ruff,Grace K. LeMasters,Grace K. LeMasters,David I. Bernstein,James E. Lockey,Timothy D. LeCras,Gurjit K. Khurana Hershey +11 more
TL;DR: It is suggested that early-life exposure to high DEP levels was associated with significantly increased asthma prevalence among allergic children but not among nonallergic children, and DEP exposure results in accumulation of allergen-specific TH2/TH17 cells in the lungs, potentiating secondary allergenic recall responses and promoting the development of allergic asthma.
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Cockroach allergen exposure and risk of asthma.
TL;DR: The epidemiological evidence for cockroachAllergen‐induced asthma, cockroach allergens, the mechanisms regarding cockroach allergenic‐induced innate immune responses, and the genetic basis forcockroach sensitization are discussed.
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