Abstract
BackgroundDifferential 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.ObjectiveThis 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.MethodsA 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 Thirty ml of venous blood was withdrawn to obtain monocyte from the patients.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.ResultsBoth 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].ConclusionDifferential 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.
Highlights
Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis
Cell surface differentiation marker profile of polarized macrophages in coronary artery disease (CAD) patients Macrophages subsets were characterized by a differential expression of cell surface markers that are generally present on macrophages including CD11b, CD14, CD86, CD80, CD206, and CD200R
No apparent CAD patients have significantly higher level of CD200R in M2 macrophages compared to M1 macrophages while M2 of non-obstructive CAD expressed significantly higher level of CD14 compared to M1 macrophages
Summary
Differential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown. Atherosclerosis is a chronic inflammatory disease described as the progressive thickening and hardening of the fatty layer in the intima media of arteries [1]. It is the predominant event that leads to coronary artery disease (CAD) where blood vessel is narrowed and blood flow is restricted [2]. There are two major phenotypes of macrophages known as M1 and M2 which involved in atherosclerosis [6, 7]. M2 macrophages is an alternatively activated macrophages induced by macrophage colony stimulating factor (MCSF), interleukin-4 (IL-4), interleukin-13 (IL13) and tumor growth factor beta (TGF-β) contributing to tissue repair and efferocytosis [11, 12]
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