Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans

• Published in: The European respiratory journal Vol. 51; no. 1; p. 1701385
• Main Authors: Mookherjee, Neeloffer, Piyadasa, Hadeesha, Ryu, Min Hyung, Rider, Christopher Francis, Ezzati, Peyman, Spicer, Victor, Carlsten, Christopher
• Format: Journal Article
• Language: English
• Published: England European Respiratory Society Journals Ltd 01.01.2018
• Subjects: Air Pollutants - adverse effects; Air pollution; Allergens; Allergens - analysis; Alveoli; Bronchi - drug effects; Bronchi - metabolism; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchus; Chromatography, Liquid; Cross-Over Studies; Cystatins; Diesel; Double-Blind Method; Enzyme-linked immunosorbent assay; Gene Expression Profiling; Humans; Hypersensitivity; Immunohistochemistry; Inflammation; Inhalation Exposure - adverse effects; Lung - metabolism; Mass Spectrometry; Normal Distribution; Oxidative Stress; Particle Size; Pollution; Proteins; Proteomics; Respiratory Hypersensitivity; Respiratory tract; Salivary Cystatins - chemistry; Secretome; Vehicle Emissions - analysis; Western blotting
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/13993003.01385-2017

Diesel exhaust (DE) is a paradigm for traffic-related air pollution. Human adaptation to DE is poorly understood and currently based on oversimplified models. DE promotes allergic responses, but protein expression changes mediated by this interaction have not been systematically investigated. The aim of this study was to define the effect of inhaled DE on allergen-induced proteins in the lung.We performed a randomised and blinded controlled human crossover exposure study. Participants inhaled filtered air or DE; thereafter, contralateral lung segments were challenged with allergen or saline. Using label-free quantitative proteomics, we comprehensively defined DE-mediated alteration of allergen-driven secreted proteins (secretome) in bronchoalveolar lavage. We further examined expression of proteins selected from the secretome data in independent validation experiments using Western blots, ELISA and immunohistochemistry.We identified protein changes unique to co-exposure (DE+allergen), undetected with mono-exposures (DE or allergen alone). Validation studies confirmed that specific proteins ( the antimicrobial peptide cystatin-SA) were significantly enhanced with DE+allergen compared to either mono-exposure.This study demonstrates that common environmental co-exposures can uniquely alter protein responses in the lungs, illuminating biology that mono-exposures cannot. This study highlights the value of complex human models in detailing airway responses to inhaled pollution.