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Morphometric analysis of inflammation in bronchial biopsies following exposure to inhaled diesel exhaust and allergen challenge in atopic subjects

Morphometric analysis of inflammation in bronchial biopsies following exposure to inhaled diesel exhaust and allergen challenge in atopic subjects
Morphometric analysis of inflammation in bronchial biopsies following exposure to inhaled diesel exhaust and allergen challenge in atopic subjects
Background

Allergen exposure and air pollution are two risk factors for asthma development and airway inflammation that have been examined extensively in isolation. The impact of combined allergen and diesel exhaust exposure has received considerably less attention. Diesel exhaust (DE) is a major contributor to ambient particulate matter (PM) air pollution, which can act as an adjuvant to immune responses and augment allergic inflammation. We aimed to clarify whether DE increases allergen-induced inflammation and cellular immune response in the airways of atopic human subjects.

Methods

Twelve atopic subjects were exposed to DE 300 ug.m-3 or filtered air for 2 h in a blinded crossover study design with a four-week washout period between arms. One hour following either filtered air or DE exposure, subjects were exposed to allergen or saline (vehicle control) via segmental challenge. Forty-eight hours post-allergen or control exposure, bronchial biopsies were collected. The study design generated 4 different conditions: filtered air+saline (FAS), DE+saline (DES), filtered air+allergen (FAA) and DE+allergen (DEA). Biopsies sections were immunostained for tryptase, eosinophil cationic protein (ECP), neutrophil elastase (NE), CD138, CD4 and interleukin (IL)-4. The percent positivity of positive cells were quantified in the bronchial submucosa.

Results

The percent positivity for tryptase expression and ECP expression remained unchanged in the bronchial submucosa in all conditions. CD4 % positive staining in DEA (0.311±0.060) was elevated relative to FAS (0.087±0.018; p=0.035). IL-4 % positive staining in DEA (0.548±0.143) was elevated relative to FAS (0.127±0.062; p=0.034). CD138 % positive staining in DEA (0.120±0.031) was elevated relative to FAS (0.017±0.006; p=0.015), DES (0.044±0.024; p=0.040), and FAA (0.044±0.008; p=0.037). CD138 % positive staining in FAA (0.044±0.008) was elevated relative to FAS (0.017±0.006; p=0.049). NE percent positive staining in DEA (0.224±0.047) was elevated relative to FAS (0.045±0.014; p=0.031).

Conclusions

In vivo allergen and DE co-exposure results in elevated CD4, IL-4, CD138 and NE in the respiratory submucosa of atopic subjects, while eosinophils and mast cells are not changed.

Trial registration

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01792232.
1743-8977
1-14
Hosseini, Ali
28188103-28f5-4802-bc6c-525a9cb05e80
Hirota, Jeremy A.
44a7c659-42fb-454b-a2e2-a494e46c4ecc
Hackett, Tillie Louise
1cf1078c-3fd6-440b-b04c-5706092eba12
McNagny, Kelly M.
9ebb920e-46b6-44cd-8048-e27cbc1182f3
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Carlsten, Chris
86f8d9b1-7691-45e0-a150-a3ea05bd2a4e
Hosseini, Ali
28188103-28f5-4802-bc6c-525a9cb05e80
Hirota, Jeremy A.
44a7c659-42fb-454b-a2e2-a494e46c4ecc
Hackett, Tillie Louise
1cf1078c-3fd6-440b-b04c-5706092eba12
McNagny, Kelly M.
9ebb920e-46b6-44cd-8048-e27cbc1182f3
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Carlsten, Chris
86f8d9b1-7691-45e0-a150-a3ea05bd2a4e

Hosseini, Ali, Hirota, Jeremy A., Hackett, Tillie Louise, McNagny, Kelly M., Wilson, Susan J. and Carlsten, Chris (2016) Morphometric analysis of inflammation in bronchial biopsies following exposure to inhaled diesel exhaust and allergen challenge in atopic subjects. Particle and Fibre Toxicology, 13 (2), 1-14. (doi:10.1186/s12989-016-0114-z). (PMID:26758251)

Record type: Article

Abstract

Background

Allergen exposure and air pollution are two risk factors for asthma development and airway inflammation that have been examined extensively in isolation. The impact of combined allergen and diesel exhaust exposure has received considerably less attention. Diesel exhaust (DE) is a major contributor to ambient particulate matter (PM) air pollution, which can act as an adjuvant to immune responses and augment allergic inflammation. We aimed to clarify whether DE increases allergen-induced inflammation and cellular immune response in the airways of atopic human subjects.

Methods

Twelve atopic subjects were exposed to DE 300 ug.m-3 or filtered air for 2 h in a blinded crossover study design with a four-week washout period between arms. One hour following either filtered air or DE exposure, subjects were exposed to allergen or saline (vehicle control) via segmental challenge. Forty-eight hours post-allergen or control exposure, bronchial biopsies were collected. The study design generated 4 different conditions: filtered air+saline (FAS), DE+saline (DES), filtered air+allergen (FAA) and DE+allergen (DEA). Biopsies sections were immunostained for tryptase, eosinophil cationic protein (ECP), neutrophil elastase (NE), CD138, CD4 and interleukin (IL)-4. The percent positivity of positive cells were quantified in the bronchial submucosa.

Results

The percent positivity for tryptase expression and ECP expression remained unchanged in the bronchial submucosa in all conditions. CD4 % positive staining in DEA (0.311±0.060) was elevated relative to FAS (0.087±0.018; p=0.035). IL-4 % positive staining in DEA (0.548±0.143) was elevated relative to FAS (0.127±0.062; p=0.034). CD138 % positive staining in DEA (0.120±0.031) was elevated relative to FAS (0.017±0.006; p=0.015), DES (0.044±0.024; p=0.040), and FAA (0.044±0.008; p=0.037). CD138 % positive staining in FAA (0.044±0.008) was elevated relative to FAS (0.017±0.006; p=0.049). NE percent positive staining in DEA (0.224±0.047) was elevated relative to FAS (0.045±0.014; p=0.031).

Conclusions

In vivo allergen and DE co-exposure results in elevated CD4, IL-4, CD138 and NE in the respiratory submucosa of atopic subjects, while eosinophils and mast cells are not changed.

Trial registration

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01792232.

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More information

Accepted/In Press date: 6 January 2016
Published date: 13 January 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 397519
URI: https://eprints.soton.ac.uk/id/eprint/397519
ISSN: 1743-8977
PURE UUID: ed57e094-1bdd-4b4c-a1fb-5a5aa5b1e76a

Catalogue record

Date deposited: 30 Jun 2016 10:59
Last modified: 09 Dec 2019 19:33

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