Abstract
Rationale: Diesel exhaust (DE), a paradigm for air pollution, is associated with respiratory diseases. Protein changes following DE exposure in humans are poorly elucidated. Objective: To define changes in the bronchial secretome following exposure to inhaled DE, using a controlled human exposure study. Methods: Mild asthmatics inhaled filtered air (FA) and DE (300 mg/m 3 ) for 2h (crossover; random order). Bronchoalveolar lavage (BAL) was obtained 48 hr after each exposure. Pooled BAL (n=5 per condition) was processed by LC-MS/MS. Protein expression intensity was determined by spectral counting. Results: Expressions of 340 secreted proteins were significantly altered in response to inhaled DE compared to FA. Expressions of 38 proteins were enhanced >4-fold in response to DE compared to FA (Fig. 1). DE-induced proteins were overrepresented in CDK5, Cdc42 and clathrin-mediated endocytosis pathways. Upstream regulators predicted to be activated were IFNA2 and retinoic acid. DE enhanced proteins related to immune processes (Fig. 1). Conclusion: This is the first comprehensive interrogation of the airway secretome following inhaled DE exposure in humans. This study details DE-driven induction of proteins related to immune responses in the bronchial environment. Fig. 1 Proteins altered by inhaled DE, interactome by Ingenuity Pathway Analysis : Red = induced by DE; Green = suppressed by DE.
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