Triggering Receptor Expressed on Myeloid Cells-2 Expression Tracks With M2-Like Macrophage Activity and Disease Severity in COPD
Triggering Receptor Expressed on Myeloid Cells-2 Expression Tracks With M2-Like Macrophage Activity and Disease Severity in COPD
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DOI：
10.1016/j.chest.2017.09.044
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发表时间：
2018-01-01
期刊：
影响因子：
9.6
通讯作者：
Holtzman, Michael J.
中科院分区：
文献类型：
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作者：
Byers, Derek E.;Wu, Kangyun;Holtzman, Michael J.
背景技术：细胞和动物模型显示髓样细胞表达的触发受体（TREM）-2在病毒感染后的慢性气道疾病中起关键作用，但仍需要建立人类的可比证据。肺组织样品获自患有慢性阻塞性肺疾病全球倡议（GOLD）IV期COPD的肺移植受者（n = 16）、不可移植的供体肺组织（n = 7）、以及从有风险或GOLD I至IV期患者中切除的肺组织（n = 55），并评估TREM-2和TREM-1信使RNA（mRNA）、蛋白质表达和其他2型免疫反应标志物。结果：与非COPD肺组织相比，GOLD IV期COPD肺组织中TREM 2（但不是TREM 1）mRNA水平增加。TREM 2 mRNA与其信号分子DAP 12和巨噬细胞标志物CD 68以及M2-巨噬细胞标志物CD 206和CHIT 1共表达。TREM-2蛋白在COPD肺组织中也增加，流式细胞术显示其定位于CD 14（+）巨噬细胞，组织免疫染色显示其定位于CD 68（+）和CCR 2（+）巨噬细胞。在来自处于风险中和患有GOLD I期至IV期COPD的患者的肺样品中，TREM 2而不是TREM 1 mRNA水平也增加，并且TREM 2/TREM 1 mRNA水平的比率与CHIT 1 mRNA的增加以及FEV 1和FEV 1/FVC的减少相关。因此，TREM-2水平和TREM-2/TREM-1的比率表示COPD肺组织中的M2活化，并且可以帮助指导针对患有这种疾病的患者中的2型免疫应答的治疗。
BACKGROUND: Cell and animal models show a key role for Triggering Receptor Expressed on Myeloid Cells (TREM)-2 in chronic airway disease after viral infection, but comparable evidence in humans still needs to be established.METHODS: Lung tissue samples were obtained from lung transplant recipients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD (n = 16), nontransplantable donor lung tissues (n = 7), and resected lung tissues from patients at risk or with GOLD stage I through IV (n = 55) and were assessed for TREM-2 and TREM-1 messenger RNA (mRNA), protein expression, and other markers of a type 2 immune response.RESULTS: TREM2 (but not TREM1) mRNA levels were increased in GOLD stage IV COPD lung tissues compared with non-COPD lung tissues. TREM2 mRNA was coexpressed with its signaling molecule DAP12 and the macrophage marker CD68 and M2-macrophage markers CD206 and CHIT1. TREM-2 protein was also increased in COPD lung tissues and was localized to CD14(+) macrophages by flow cytometry and CD68(+) and CCR2(+) macrophages by tissue immunostaining. In lung samples from patients at risk and with GOLD stage I through IV COPD, TREM2 but not TREM1 mRNA levels were also increased, and the ratio of TREM2/TREM1 mRNA levels was associated with increases in CHIT1 mRNA and decreases in FEV1 and FEV1/FVC.CONCLUSIONS: TREM-2 expression is increased in lung macrophages in COPD, particularly in comparison with TREM-1. Therefore, TREM-2 levels and the ratio of TREM-2/TREM-1 signifies M2 activation in COPD lung tissues and may help to guide therapeutics directed against the type 2 immune response in patients with this disease.