Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan.
Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 23142, Taiwan.
Medicina (Kaunas). 2021 Jul 30;57(8):778. doi: 10.3390/medicina57080778.
: Tumor progression and the immune response are intricately linked. Additionally, the presence of macrophages in the microenvironment is essential for carcinogenesis, but regulation of the polarization of M1- and M2-like macrophages and their role in metastasis remain unclear. Based on previous studies, both reactive oxygen species (ROS) and the endoplasmic reticulum (ER) are emerging as key players in macrophage polarization. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, there is limited knowledge regarding how they affect the macrophage-dependent innate host defense. : We detected the levels of ROS, the ability of chemotaxis, the expressions of markers of M1-/M2-like macrophages in RAW264.7 in presence of T2- and T2C-conditioned medium. : The results of this study indicated that ROS levels were decreased in RAW 264.7 cells when cultured with T2C-conditioned medium, while there was an improvement in chemotaxis abilities. We also found that the M2-like macrophages were characterized by an elongated shape in RAW 264.7 cells cultured in T2C-conditioned medium, which had increased CD206 expression but decreased expression of CD86 and inducible nitric oxide synthase. Suppression of ER stress shifted polarized M1-like macrophages toward an M2-like phenotype in RAW 264.7 cells cultured in T2C-conditioned medium. : Taken together, we conclude that the polarization of macrophages is associated with the alteration of cell shape, ROS accumulation, and ER stress.
肿瘤的发生发展与机体的免疫反应密切相关。此外，巨噬细胞在肿瘤微环境中的存在对于癌症的发生发展是必需的，但 M1 型和 M2 型巨噬细胞极化的调控及其在转移中的作用仍不清楚。基于既往研究，活性氧（ROS）和内质网（ER）均被认为是巨噬细胞极化的关键因素。尽管已知癌症会改变巨噬细胞的炎症反应，从而促进肿瘤的发生发展，但对于它们如何影响依赖巨噬细胞的固有宿主防御的了解还很有限。
我们检测了 RAW264.7 细胞中 ROS 水平、趋化能力以及 M1/M2 型巨噬细胞标志物的表达，这些细胞在 T2 和 T2C 条件培养基中培养。
本研究结果表明，当用 T2C 条件培养基培养 RAW264.7 细胞时，ROS 水平降低，而趋化能力增强。我们还发现，在 T2C 条件培养基中培养的 RAW264.7 细胞中，M2 型巨噬细胞呈长梭形，CD206 表达增加，而 CD86 和诱导型一氧化氮合酶表达降低。在 T2C 条件培养基中培养的 RAW264.7 细胞中，抑制 ER 应激可使极化的 M1 型巨噬细胞向 M2 型表型转化。
综上所述，我们得出结论，巨噬细胞的极化与细胞形态的改变、ROS 积累和 ER 应激有关。
