Center for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
BMC Pulm Med. 2018 Jun 15;18(1):101. doi: 10.1186/s12890-018-0664-y.
The ability of circulating monocytes to develop into lung macrophages and promote lung tissue damage depends upon their phenotypic pattern of differentiation and activation. Whether this phenotypic pattern varies with COPD severity is unknown. Here we characterize the activation and differentiation status of circulating monocytes in patients with moderate vs. severe COPD.
Blood monocytes were isolated from normal non-smokers (14), current smokers (13), patients with moderate (9), and severe COPD (11). These cells were subjected to analysis by flow cytometry to characterize the expression of activation markers, chemoattractant receptors, and surface markers characteristic of either M1- or M2-type macrophages.
Patients with severe COPD had increased numbers of total circulating monocytes and non-classical patrolling monocytes, compared to normal subjects and patients with moderate COPD. In addition, while the percentage of circulating monocytes that expressed an M2-like phenotype was reduced in patients with either moderate or severe disease, the levels of expression of M2 markers on this subpopulation of monocytes in severe COPD was significantly elevated. This was particularly evident for the expression of the chemoattractant receptor CCR5.
Blood monocytes in severe COPD patients undergo unexpected pre-differentiation that is largely characteristic of M2-macrophage polarization, leading to the emergence of an unusual M2-like monocyte population with very high levels of CCR5. These results show that circulating monocytes in patients with severe COPD possess a cellular phenotype which may permit greater mobilization to the lung, with a pre-existing bias toward a potentially destructive inflammatory phenotype.
循环单核细胞发展为肺巨噬细胞并促进肺组织损伤的能力取决于其分化和激活的表型模式。这种表型模式是否随 COPD 严重程度而变化尚不清楚。在这里，我们描述了中度与重度 COPD 患者循环单核细胞的激活和分化状态。
从正常非吸烟者（14 例）、当前吸烟者（13 例）、中度 COPD 患者（9 例）和重度 COPD 患者（11 例）中分离血液单核细胞。通过流式细胞术分析这些细胞，以描述激活标志物、趋化因子受体和特征性 M1 或 M2 型巨噬细胞的表面标志物的表达。
与正常受试者和中度 COPD 患者相比，重度 COPD 患者的总循环单核细胞和非经典巡弋单核细胞数量增加。此外，虽然中度或重度疾病患者的循环单核细胞中表达 M2 样表型的比例降低，但该亚群单核细胞上 M2 标志物的表达水平在重度 COPD 中显著升高。这在趋化因子受体 CCR5 的表达上尤为明显。
重度 COPD 患者的血液单核细胞经历了出乎意料的预分化，主要表现为 M2 型巨噬细胞极化，导致出现一种具有非常高水平 CCR5 的异常 M2 样单核细胞群体。这些结果表明，重度 COPD 患者循环单核细胞具有一种可能允许向肺部更大程度动员的细胞表型，并且预先存在偏向潜在破坏性炎症表型的倾向。
