Effect of diesel emissions on human airway epithelial cells

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that affects more than 250 million people worldwide. COPD exacerbations are linked to exposure to diesel exhaust (DE). DE constitutes the largest portion of air pollution in urbanized areas. The lung epithelium is the first site of interaction between inhaled substances and the human body and it is built to function as a physical and immunological barrier. The in vitro model proposed in this thesis was designed to reproduce as much as possible the dynamics of exposure of the lung epithelium to DE in real life. Highly differentiated cultures of bronchial epithelial cells from patients were exposed to freshly produced DE from a Euro I generator or a Euro V bus engine. Activation of oxidant and integrated stress responses upon exposure to the emission of the Euro I diesel generator in lung epithelial cells was rapid and transient. DE exposures were followed by treatment with UV-inactivated non-typeable Haemophilus influenzae (NTHi), a bacterium highly associated with COPD exacerbations. For the first time, inhibition of the antimicrobial response by diesel exhaust was demonstrated in primary bronchial epithelial cells. Bronchial epithelial cells responded in a similar way to diesel exhaust and cigarette smoke.