title: Diesel exhaust particle exposure in vitro alters monocyte differentiation and function.
abstract: Air pollution by diesel exhaust particles is associated with elevated mortality and increased hospital admissions in individuals with respiratory diseases such as asthma and chronic obstructive pulmonary disease. During active inflammation monocytes are recruited to the airways and can replace resident alveolar macrophages. We therefore investigated whether chronic fourteen day exposure to low concentrations of diesel exhaust particles can alter the phenotype and function of monocytes from healthy individuals and those with chronic obstructive pulmonary disease. Monocytes were purified from the blood of healthy individuals and people with a diagnosis of chronic obstructive pulmonary disease. Monocyte-derived macrophages were generated in the presence or absence of diesel exhaust particles and their phenotypes studied through investigation of their lifespan, cytokine generation in response to Toll like receptor agonists and heat killed bacteria, and expression of surface markers. Chronic fourteen day exposure of monocyte-derived macrophages to concentrations of diesel exhaust particles >10 µg/ml caused mitochondrial and lysosomal dysfunction, and a gradual loss of cells over time both in healthy and chronic obstructive pulmonary disease individuals. Chronic exposure to lower concentrations of diesel exhaust particles impaired CXCL8 cytokine responses to lipopolysaccharide and heat killed E. coli, and this phenotype was associated with a reduction in CD14 and CD11b expression. Chronic diesel exhaust particle exposure may therefore alter both numbers and function of lung macrophages differentiating from locally recruited monocytes in the lungs of healthy people and patients with chronic obstructive pulmonary disease.
authors.affiliation: Academic Unit of Respiratory Medicine, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Nazia
authors.initials: N
authors.lastname: Chaudhuri
authors.forename: Hannah
authors.initials: H
authors.lastname: Jary
authors.forename: Simon
authors.initials: S
authors.lastname: Lea
authors.forename: Naimat
authors.initials: N
authors.lastname: Khan
authors.forename: Katie C
authors.initials: KC
authors.lastname: Piddock
authors.forename: David H
authors.initials: DH
authors.lastname: Dockrell
authors.forename: Ken
authors.initials: K
authors.lastname: Donaldson
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Parker
authors.forename: Ian
authors.initials: I
authors.lastname: Sabroe
mesh_terms: D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive; D001335:Vehicle Emissions
chemical_list: D016207:Cytokines; D001335:Vehicle Emissions