Abstract
Rationale: Diesel exhaust (DE) exposure increases lung inflammation and promotes asthma progression. However, molecular changes after allergen-DE co-exposure are poorly elucidated.
Objective: To define changes in the allergen-induced bronchial secretome enhanced by DE.
Methods: Five mild asthmatics inhaled filtered air (FA) or DE (300 mg/m3) for 2h, in a randomized, blinded, controlled human crossover study. Lung segments were subsequently challenged with allergen (A) or saline and bronchoalveolar lavage (BAL) obtained 48h later. After 4 weeks, 2nd study arms were completed. Pooled BAL was processed by LC-MS/MS using a label-free quantitative approach.
Results: 76 secreted proteins (of 2122 across all three conditions) in FA-A were significantly altered in DE-A (Fig. 1), with C4B, LCN1, MUC16, TCN1 and CST2 enhanced >4-fold following co-exposure. Network analyses showed that DE-altered protein clusters included those related to retinoid nuclear receptors, nitric oxide/ROS, Rho GTPases and AKT/PI3K signaling.
Conclusion: This first comprehensive interrogation of the airway secretome following DE/allergen co-exposure in humans showed that DE impacted allergen-induced responses by altering key biological processes such as lipid metabolism, oxidative stress and inflammation. : Co-exposure with DE alters allergen-induced secreted proteins in BAL. A-induced proteins: Green-enhanced, Blue-unchanged, or Pink-suppressed, by DE.
- Copyright ©the authors 2016
