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The effects of diesel exhaust on neutrophil functions in never-smokers, ex-smokers, and COPD patients Wooding, Denise

Abstract

Introduction: Traffic-related air pollution (TRAP) is associated with COPD epidemiologically, however the mechanism of this interaction remains unclear. Neutrophils, a key inflammatory cell in COPD, migrate to the lungs following TRAP exposure, but their functional role in this response is poorly understood. The aim of this study is to elucidate the effects of TRAP exposure on neutrophil function, using the model of diesel exhaust (DE). Methods: In vitro: Isolated peripheral blood neutrophils were incubated with diesel exhaust particles (DEPs) before quantifying activation marker expression, oxidative burst, and neutrophil extracellular traps (NETs). In vivo: Subjects from three groups (never-smokers, ex-smokers, and mild-moderate COPD) participated in a randomized double-blind controlled human exposure crossover study. Subjects were exposed on one occasion to filtered air and on another occasion to diluted DE. Blood and bronchoalveolar lavage (BAL) samples were used to assess the effect of DE on the number and function of pulmonary and systemic neutrophils. Results: DEPs increased CD66b, oxidative burst, and NET formation in vitro. Controlled human exposure to DE reduced the proportion of circulating band cells, increased NET formation in BAL, and resulted in lymphocytic but not neutrophilic inflammation. The effect of DE on band cells and peripheral CD182 expression was distinct in the COPD group. There was no effect on oxidative burst or activation marker expression in pulmonary neutrophils. Conclusion: Diesel exhaust increases some, but not all, neutrophil effector activities in vitro and in vivo. Two potential mechanisms for susceptibility in COPD patients were identified. These results demonstrate a functional role for neutrophils in the inflammatory response to diesel exhaust. The potential for DE-induced neutrophil activity to promote lung tissue damage and clinical features of COPD may be an area of future investigation.

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