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Diesel exhaust particle exposure increases severity of allergic asthma in young mice.
Clin Exp Allergy 2013; 43(12):1406-18CE

Abstract

BACKGROUND

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-17(pos) and IL-13(pos) /IL-17A(pos) 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-17(pos) and IL-13(pos) /IL-17A(pos) 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.

Authors+Show Affiliations

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24112543

Citation

Acciani, T H., et al. "Diesel Exhaust Particle Exposure Increases Severity of Allergic Asthma in Young Mice." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 43, no. 12, 2013, pp. 1406-18.
Acciani TH, Brandt EB, Khurana Hershey GK, et al. Diesel exhaust particle exposure increases severity of allergic asthma in young mice. Clin Exp Allergy. 2013;43(12):1406-18.
Acciani, T. H., Brandt, E. B., Khurana Hershey, G. K., & Le Cras, T. D. (2013). Diesel exhaust particle exposure increases severity of allergic asthma in young mice. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 43(12), pp. 1406-18. doi:10.1111/cea.12200.
Acciani TH, et al. Diesel Exhaust Particle Exposure Increases Severity of Allergic Asthma in Young Mice. Clin Exp Allergy. 2013;43(12):1406-18. PubMed PMID: 24112543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diesel exhaust particle exposure increases severity of allergic asthma in young mice. AU - Acciani,T H, AU - Brandt,E B, AU - Khurana Hershey,G K, AU - Le Cras,T D, PY - 2013/04/15/received PY - 2013/07/30/revised PY - 2013/09/16/accepted PY - 2013/10/12/entrez PY - 2013/10/12/pubmed PY - 2014/7/19/medline KW - T cells KW - Th17 KW - Th2 KW - air pollution KW - allergen KW - asthma KW - atopy KW - dendritic cells KW - diesel exhaust particle KW - house dust mite SP - 1406 EP - 18 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 43 IS - 12 N2 - BACKGROUND: 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-17(pos) and IL-13(pos) /IL-17A(pos) 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-17(pos) and IL-13(pos) /IL-17A(pos) 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. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/24112543/Diesel_exhaust_particle_exposure_increases_severity_of_allergic_asthma_in_young_mice_ L2 - https://doi.org/10.1111/cea.12200 DB - PRIME DP - Unbound Medicine ER -