School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
Faculty of Veterinary Medicine, Universiti Malaysia Kelantan, 16100, Pengkalan Chepa, Kelantan, Malaysia.
BMC Immunol. 2021 Mar 24;22(1):21. doi: 10.1186/s12865-021-00410-2.
Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.
This study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.
A total of 14 (n) CAD patients were recruited and subsequently grouped into "no apparent CAD", "non-obstructive CAD" and "obstructive CAD" according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86/CD80 for M1 and CD206/CD200R for M2) and measurement of MerTK expression were performed using flow cytometry.
Both M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].
Differential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.
巨噬细胞向 M1 和 M2 极化介导通过吞噬作用清除动脉粥样硬化斑块。M2 巨噬细胞上 Mer 原癌基因酪氨酸激酶（MerTK）的高表达有助于维持巨噬细胞的吞噬作用效率。在健康个体中，巨噬细胞向 M1 和 M2 的极化发生在组织中，同时根据特定的微环境刺激获得功能表型。然而，冠心病（CAD）患者的巨噬细胞极化和 MerTK 表达是否存在差异仍不清楚。
本研究旨在阐明 CAD 患者的 M1 和 M2 巨噬细胞极化，并研究这些巨噬细胞表型中 MerTK 的表达。
共招募了 14 名（n）CAD 患者，并根据狭窄程度将其分为“无明显 CAD”、“非阻塞性 CAD”和“阻塞性 CAD”。从患者中抽取 30ml 静脉血获得单核细胞。用 GMCSF、LPS 和 IFN-γ 处理单核细胞生成 M1 巨噬细胞，用 MCSF、IL-4 和 IL-13 将单核细胞分化为 M2 巨噬细胞。极化 7 天后，使用流式细胞术分析细胞表面分化标志物（M1 上的 CD86/CD80 和 M2 上的 CD206/CD200R）和 MerTK 表达的测量。
在所有 CAD 患者组中，M1 和 M2 巨噬细胞均表达相似水平的 CD86、CD80 和 CD206。无明显 CAD 患者中，M2 巨噬细胞中的 MerTK 表达明显高于 M1 巨噬细胞[12.58±4.40 对 6.58±1.37，p=0.040]。
由于动脉粥样硬化斑块中的微环境刺激，巨噬细胞向 M1 和 M2 的极化具有高度动态性，可以发生变化。此外，在阻塞性最低的患者中 MerTK 的高表达表明其在吞噬作用中具有重要作用。
