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Updated: Jun 23, 2025
An In vitro Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization
Published on: June 12, 2013
The effect of ox-LDL and platelets on macrophages, M2 macrophage polarization, and foam cell formation
Fatemeh Barati1, Davood Bashash1, Mohamad Hosein Mohamadi2
1Department of Hematology and Blood Banking, School of Allied Medical Sciences Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background:
The accumulation of oxidized LDL (ox-LDL) in macrophages in association with platelet activity leads to the formation of foam cells, which play a key role in the pathophysiology of atherosclerosis and coronary artery diseases (CAD). Here, in this study, we aimed to investigate the simultaneous effect of ox-LDL and platelets on foam cell formation, as well as modification in cell markers.
Method:
First, the U937, a human monocytic cell line, was cultured in RPMI-1640. Then, isolated platelets were co-cultured with the U937 and exposed to ox-LDL (80 µg/ml) to evaluate the impact of ox-LDL on foam cell formation using Oil red O (ORO) staining. Also, the expression of foam cells' surface markers and CD36, ABCA1, SR-B1, ACAT1, and LXRα genes, which are involved in macrophage metabolism and ox-LDL uptake, was measured by flow cytometry and real-time PCR, respectively.
Results:
Our findings suggest that platelets promoted foam cell formation (ORO-positive cells), accompanied by a higher level of CD163+ M2 macrophages. Furthermore, the expression of CD36, ABCA1, SR-B1, ACAT1, and LXRα genes, which are implicated in cholesterol accumulation in macrophages, was significantly upregulated in the ox-LDL+ platelets group compared to the control (P < 0.05). Moreover, the up-regulation of CD36, ABCA1, and SR-B1 genes in the ox-LDL+ platelets group was more accentuated compared to the ox-LDL group (P < 0.05).
Conclusions:
Owing to the positive effector role of platelets in the formation of foam cells and CD163+ cells, it could be assumed that platelets play a dual role in the development of these cells.
