COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils

Abstract

BackgroundEosinophilic airway inflammation is observed in 10-30% of COPD subjects. Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown.MethodsWe categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (≥3%/year). Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls.ResultsThere were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n = 10), B-high red hue, high sputum eosinophils (n = 16), C-low red hue, low sputum eosinophils (n = 19) and D- high red hue, low sputum eosinophils (n = 58). Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p = 0.01). The fall in FEV1 from stable to exacerbation was greatest in group A (ΔFEV1 [95 % CI] -0.41 L [-0.65 to -0.17]) versus group B (-0.16 L [-0.32 to -0.011]), C (-0.11 L [-0.23 to -0.002]) and D (-0.16 L [-0.22 to -0.10]; p = 0.02). Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p = 0.028); was most marked in group A (71 [70 to 84]%; p = 0.0295) and was inversely correlated with exacerbation frequency (r = -0.63; p = 0.006).ConclusionsMacrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations.

Pulmonary macrophages: key players in the innate defence of the airways

“…AMs from patients with COPD exhibit impaired induction of TLR2 expression after incubation in vitro with Moraxella catarrhalis , Streptococcus pneumoniae or Haemophilus influenza. 39 Furthermore, COPD-AMs exhibit a reduced ability to phagocytose apoptotic epithelial cells,40 eosinophils41 and bacteria 42. Lung parenchymal destruction is a key feature of COPD and macrophages have been shown to directly contribute to this process.…”

Lung Macrophage Functional Properties in Chronic Obstructive Pulmonary Disease

“…Removing cell debris and eliminating cells undergoing programmed cell death are crucial processes in containing ongoing inflammation and the resolution of inflammation [103,104]. LMs from COPD patients and CS-treated animals have decreased ingested apoptotic cells [105] and microorganisms, such as Haemophilus influenzae [24,[106][107][108][109], Candida albicans [110,111], Escherichia coli, Moraxella catarrhalis [106,107], and Streptococcus pneumoniae [24,106,112], apoptotic neutrophils [113,114], eosinophils [115], and airway epithelial cells [116][117][118]. Interestingly, LMs from COPD patients have similar phagocytosic activities of inert beads than cells from control subjects [109,118], indicatings that CS does not cause a generalized impairment in phagocytic capacity of LMs.…”

<p>How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?</p>

“…The innate immune cells surround the respiratory membranes and interact with the pulmonary microcirculation. The major differences in cell components of the small airways include: (1) senescence of epithelial cells, 21 destruction and fibrosis of peribronchiolar and alveolar walls; 22 (2) a marked increase in the number of neutrophils, which is correlated with the severity of airflow obstruction; 23 (3) increased number of macrophages with impaired phagocytosis and efferocytosis; 24,25 (4) increased number of CD8 + T and CD4 + T lymphocytes; 26 and (5) increased number and activation of epithelial DCs. 27 In the small airways, lymphoid aggregates (LAs) can be found in the outer layer of the small vessels, as well as in the adventitia of bronchioles, and the alveolar lumen.…”