Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Biochem Biophys Res Commun. 2024 Nov 12;733:150697. doi: 10.1016/j.bbrc.2024.150697. Epub 2024 Sep 13.
Macrophages, abundant in tumors, are classified as M1 or M2 types with M2 dominating the tumor microenvironment. Shifting macrophages from M2 to M1 using exosomes is a promising intervention. The properties of exosomes depend on their source cells. M1-exosomes are expected to polarize macrophages towards M1 phenotype. We compared M1-exosomes and M0-exosomes' effects on M2 macrophage polarization. The RAW264.7 cells were cultured and one group of them was exposed to LPS. The serum-free medium was collected and exosomes were extracted. Exosomes were analyzed by scanning and transmission electron microscopy, dynamic light scattering and Western blot. Subsequently, M1 or M0 exosomes were applied to M2 macrophages induced by IL4. The macrophages polarization, including M1 and M2 genes and surface markers expression, cytokines secretion, and phagocytosis ability were evaluated. It was demonstrated that M1-exosomes induced macrophage polarization toward the M1 phenotype, characterized by an upregulation of M1-specific markers and a downregulation of M2 markers. Furthermore, the secretion of TNF-α was increased, while the secretion of IL-10 was decreased. The phagocytosis ability of M1-exosome-treated macrophages was also augmented. This research suggested that M1-exosomes might be promising candidates for modulating immune response in situations marked by an overabundance of M2 polarization, like in cancer.
巨噬细胞在肿瘤中丰富，分为 M1 或 M2 型，M2 型在肿瘤微环境中占主导地位。使用外泌体将巨噬细胞从 M2 型转变为 M1 型是一种很有前途的干预方法。外泌体的特性取决于其来源细胞。M1-外泌体有望使巨噬细胞向 M1 表型极化。我们比较了 M1-外泌体和 M0-外泌体对 M2 巨噬细胞极化的影响。培养 RAW264.7 细胞，其中一组用 LPS 处理。收集无血清培养基并提取外泌体。通过扫描和透射电子显微镜、动态光散射和 Western blot 分析外泌体。随后，将 M1 或 M0 外泌体应用于由 IL4 诱导的 M2 巨噬细胞。评估巨噬细胞极化，包括 M1 和 M2 基因和表面标志物表达、细胞因子分泌和吞噬能力。结果表明，M1-外泌体诱导巨噬细胞向 M1 表型极化，其特征是 M1 特异性标志物上调和 M2 标志物下调。此外，TNF-α 的分泌增加，而 IL-10 的分泌减少。M1-外泌体处理的巨噬细胞的吞噬能力也增强。这项研究表明，M1-外泌体可能是调节免疫反应的有前途的候选物，特别是在 M2 极化过度的情况下，如癌症。
