Impaired macrophage phagocytosis of bacteria in severe asthma.

Zhike Liang,Louise E Donnelly,Kirandeep K Chana,Catherine Mr Thomas,Pankaj K Bhavsar,Kian Fan Chung,David Gibeon,Peter J Barnes,Qingling Zhang

doi:10.1186/1465-9921-15-72

Abstract

BackgroundBacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria.MethodsPhagocytosis of fluorescently-labelled polystyrene beads, Haemophilus influenzae or Staphylococcus aureus by broncholaveolar lavage alveolar macrophages (AM) and by monocyte-derived macrophages (MDM) from non-asthmatics, mild-moderate and severe asthmatic patients was assessed using fluorimetry.ResultsThere were no differences in phagocytosis of polystyrene beads by AMs or MDMs from any of the subject groups. There was reduced phagocytosis of Haemophilus influenzae and Staphylococcus aureus in MDMs from patients with severe asthma compared to non-severe asthma (p < 0.05 and p < 0.01, respectively) and healthy subjects (p < 0.01and p < 0.001, respectively). Phagocytosis of Haemophilus influenzae and Staphylococcus aureus by AM was also reduced in severe asthma compared to normal subjects (p < 0.05). Dexamethasone and formoterol did not suppress phagocytosis of bacteria by MDMs from any of the groups.ConclusionsPersistence of bacteria in the lower airways may result partly from a reduced phagocytic capacity of macrophages for bacteria. This may contribute to increased exacerbations, airway colonization and persistence of inflammation.

Highlights

Patients with asthma are usually well-controlled with inhaled corticosteroids (CS) and long-acting β2-agonists, but a proportion of patients, described as severe asthmatics, continue to experience uncontrolled asthma in spite of these treatments [1]
In the severe asthmatics recruited to the alveolar macrophages (AM) study (Table 2), there was a trend towards higher eosinophil and neutrophils counts in bronchoalveolar lavage (BAL) compared to both healthy and non-severe asthmatic subjects
There was impaired phagocytosis of fluorescently-labelled H. influenzae by monocyte-derived macrophages (MDM) from severe asthmatics compared to cells from non-severe asthmatic patients (p < 0.05) and normal subjects (p < 0.01; Figure 1B)

Summary

Introduction

Patients with asthma are usually well-controlled with inhaled corticosteroids (CS) and long-acting β2-agonists, but a proportion of patients, described as severe asthmatics, continue to experience uncontrolled asthma in spite of these treatments [1]. Viral and bacterial infections or colonization with bacteria could lead to chronic lower airway inflammation, impaired. Defective efferocytosis by AMs from severe asthmatics but not from mildmoderate asthmatics has been reported [13]. This defect has been postulated to underlie the chronic inflammatory state due to the accumulation of bacteria and apoptotic and necrotic cells in the airways. In chronic obstructive pulmonary disease (COPD), a number of studies have shown defects in both bacterial clearance [14,15] and efferocytosis [16] indicating impaired macrophage innate responses. Bacteria are frequently cultured from sputum samples of severe asthma patients suggesting a defect in bacterial clearance from the airway. We measured the capacity of macrophages from patients with asthma to phagocytose bacteria

Methods

Results

Conclusion