Defective macrophage phagocytosis of bacteria in COPD

¹ Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse St, London, SW3 6LY, UK
² Academic Unit of Respiratory Medicine, Royal Free and University College Medical School, University College London, UK

^* To whom correspondence should be addressed. E-mail: l.donnelly{at}imperial.ac.uk.

	Abstract

Exacerbations of chronic obstructive pulmonary disease (COPD) are an increasing cause of hospitalizations and are associated with accelerated progression of airflow obstruction. Approximately half of COPD exacerbations are associated with bacteria and many patients have lower airways colonization. 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) were 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 non-smokers. MDM from COPD patients showed reduced phagocytic responses to S.pneumoniae and H. influenzae compared with non-smokers and smokers. This was not associated with alterations in cell surface receptor expression of TLR2, TLR4, MARCO, CD163, CD36 or the 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.