title: Defective macrophage phagocytosis of bacteria in COPD.
abstract: Exacerbations of chronic obstructive pulmonary disease (COPD) are an increasing cause of hospitalisations and are associated with accelerated progression of airflow obstruction. Approximately half of COPD exacerbations are associated with bacteria and many patients have lower airways colonisation. This suggests that bacterial infection in COPD could be due to reduced pathogen removal. This study investigated whether bacterial clearance by macrophages is defective in COPD. Phagocytosis of fluorescently labelled polystyrene beads and Haemophillus influenzae and Streptococcus pneumoniae by alveolar macrophages and monocyte-derived macrophages (MDM) was assessed by fluorimetry and flow cytometry. Receptor expression was measured by flow cytometry. Alveolar macrophages and MDM phagocytosed polystyrene beads similarly. There was no difference in phagocytosis of beads by MDM from COPD patients compared with cells from smokers and nonsmokers. MDM from COPD patients showed reduced phagocytic responses to S. pneumoniae and H. influenzae compared with nonsmokers and smokers. This was not associated with alterations in cell surface receptor expression of toll-like receptor (TLR)2, TLR4, macrophage receptor with collagenous structure, cluster of differentiation (CD)163, CD36 or mannose receptor. Budesonide, formoterol or azithromycin did not suppress phagocytosis suggesting that reduced responses in COPD MDM were not due to medications. COPD macrophage innate responses are suppressed and may lead to bacterial colonisation and increased exacerbation frequency.
authors.affiliation: Airways Disease Section, National Heart and Lung Institute, Dovehouse Street, London, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Taylor
authors.forename: T K
authors.initials: TK
authors.lastname: Finney-Hayward
authors.forename: J K
authors.initials: JK
authors.lastname: Quint
authors.forename: C M R
authors.initials: CM
authors.lastname: Thomas
authors.forename: S J
authors.initials: SJ
authors.lastname: Tudhope
authors.forename: J A
authors.initials: JA
authors.lastname: Wedzicha
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: L E
authors.initials: LE
authors.lastname: Donnelly
mesh_terms: D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005470:Fluorometry; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D050296:Microbial Viability; D018613:Microscopy, Confocal; D008875:Middle Aged; D010587:Phagocytosis / Q000276:immunology*; D011137:Polystyrenes; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000276:immunology
chemical_list: D011137:Polystyrenes