Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Medical Department, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
J Transl Med. 2018 Mar 15;16(1):69. doi: 10.1186/s12967-018-1435-5.
Controversy exists in previous studies on macrophage M1/M2 polarization in chronic obstructive pulmonary disease (COPD). We hypothesized that formyl peptide receptor (FPR), a marker of efferocytosis and mediator of M1/M2 polarization, may be involved in the development of COPD.
We examined FPR 1/2/3 expressions of blood M1/M2a monocyte, neutrophil, natural killer (NK) cell, NK T cell, T helper (Th) cell, and T cytotoxic (Tc) cell by flowcytometry method in 40 patients with cigarette smoking-related COPD and 16 healthy non-smokers. Serum levels of five FPR ligands were measured by ELISA method.
The COPD patients had lower M2a percentage and higher percentages of NK, NK T, Th, and Tc cells than the healthy non-smokers. FPR2 expressions on Th/Tc cells, FPR3 expressions of M1, M2a, NK, NK T, Th, and Tc cells, and serum annexin A1 (an endogenous FPR2 ligand) levels were all decreased in the COPD patients as compared with that in the healthy non-smokers. FPR1 expression on neutrophil was increased in the COPD patient with a high MMRC dyspnea scale, while FPR2 expression on neutrophil and annexin A1 were both decreased in the COPD patients with a history of frequent moderate exacerbation (≥ 2 events in the past 1 year). In 10 COPD patients whose blood samples were collected again after 1-year treatment, M2a percentage, FPR3 expressions of M1/NK/Th cells, FPR2 expression on Th cell, and FPR1 expression on neutrophil were all reversed to normal, in parallel with partial improvement in small airway dysfunction.
Our findings provide evidence for defective FPR2/3 and annexin A1 expressions that, associated with decreased M2a polarization, might be involved in the development of cigarette smoking induced persistent airflow limitation in COPD.
慢性阻塞性肺疾病（COPD）中巨噬细胞 M1/M2 极化的相关研究存在争议。我们假设趋化因子受体（FPR），作为吞噬作用的标志物和 M1/M2 极化的介质，可能参与 COPD 的发生发展。
我们采用流式细胞术检测了 40 例吸烟相关 COPD 患者和 16 例健康非吸烟者外周血 M1/M2a 单核细胞、中性粒细胞、自然杀伤（NK）细胞、NK T 细胞、辅助性 T 细胞（Th）和细胞毒性 T 细胞（Tc）中 FPR1/2/3 的表达，并采用 ELISA 法检测了五种 FPR 配体的血清水平。
与健康非吸烟者相比，COPD 患者 M2a 比例较低，NK、NK T、Th 和 Tc 细胞比例较高。与健康非吸烟者相比，COPD 患者 Th/Tc 细胞上的 FPR2 表达、M1、M2a、NK、NK T、Th 和 Tc 细胞上的 FPR3 表达以及血清膜联蛋白 A1（一种内源性 FPR2 配体）水平均降低。COPD 患者中，高 MMRC 呼吸困难量表患者的中性粒细胞 FPR1 表达增加，而频繁发生中度加重（过去 1 年中发生≥2 次）的 COPD 患者的中性粒细胞 FPR2 表达和膜联蛋白 A1 表达均降低。在 10 例接受 1 年治疗后再次采集血液样本的 COPD 患者中，M2a 比例、M1/NK/Th 细胞的 FPR3 表达、Th 细胞上的 FPR2 表达和中性粒细胞上的 FPR1 表达均恢复正常，同时小气道功能障碍得到部分改善。
我们的研究结果为 FPR2/3 和膜联蛋白 A1 表达缺陷提供了证据，这种缺陷与 M2a 极化减少有关，可能参与了吸烟引起的 COPD 持续气流受限的发生发展。
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