Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients

• Published in: BMC immunology 2021-03, Vol.22 (1), p.21-21, Article 21
• Main Authors: Mohd Idrus, Fatin Najiah, Ahmad, Nurul Shuhadah, Hoe, Chee Hock, Azlan, Maryam, Norfuad, Farisha Alia, Yusof, Zurkurnai, Wan Isa, Wan Yus Haniff, Mohamed Ali, Akbar Ali, Yvonne-Tee, Get Bee
• Format: Article
• Language: English
• Subjects: Adult; Arteriosclerosis; Atherosclerosis; c-Mer Tyrosine Kinase - metabolism; Cardiovascular disease; Carotid arteries; CD80 antigen; CD86 antigen; Cell Differentiation; Cell surface; Cell surface differentiation marker; Cellular Microenvironment; Coronary artery; Coronary artery disease; Coronary Artery Disease - immunology; Coronary heart disease; Coronary vessels; Coronary Vessels - pathology; Cytokines; Cytokines - metabolism; Development and progression; Efferocytosis; Endocytosis; Female; Flow Cytometry; Genetic aspects; Health aspects; Heart diseases; Humans; Interleukin 13; Interleukin 4; Macrophage polarization; Macrophages; Macrophages - immunology; Male; Mer proto-oncogene tyrosine kinase; Microenvironments; Middle Aged; Monocytes; Pathogens; Patients; Phagocytosis; Phenotypes; Polarization; Protein tyrosine kinase; Stenosis; Th1 Cells - immunology; Th2 Cells - immunology; Tumor necrosis factor-TNF; Up-Regulation; γ-Interferon
• ISSN: 1471-2172; 1471-2172
• 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 Thirty ml of venous blood was withdrawn to obtain monocyte from the patients.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.