LATE-BREAKING ABSTRACT: Inhaled diesel exhaust alters immune response proteins in the bronchial secretome in humans

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 secretomefollowing exposure to inhaledDE, using a controlled human exposure study. Methods: Mild asthmatics inhaledfiltered 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 inhaledDE 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, Cdc42and clathrin-mediated endocytosis pathways. Upstream regulators predicted to be activated were IFNA2and retinoic acid. DE enhanced proteins related to immune processes (Fig. 1). Conclusion: This is the first comprehensive interrogation of the airway secretomefollowing inhaledDE exposure in humans. This study details DE-driven induction of proteins related to immune responses in the bronchial environment. Fig. 1 Proteins altered by inhaledDE, interactomeby Ingenuity Pathway Analysis: Red = induced by DE; Green = suppressed by DE.