Na Yi Rang, Hong Ji Hye, Lee Min Yong, Jung Jae Hun, Jung Daun, Kim Young Won, Son Dain, Choi Murim, Kim Kwang Pyo, Seok Seung Hyeok
From the ‡Department of Microbiology and Immunology, and Institute of Endemic Disease, Seoul National University College of Medicine, 103 Daehak-ro, Chongno-gu, Seoul 110-799, South Korea;
§Department of Applied Chemistry, Kyung Hee University, 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 446-701, South Korea;
Mol Cell Proteomics. 2015 Oct;14(10):2722-32. doi: 10.1074/mcp.M115.048744. Epub 2015 Jul 30.
Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs.
巨噬细胞在控制感染因子和维持组织内稳态方面至关重要。巨噬细胞需要多种功能能力才能在我们的身体中发挥不同作用，其中之一是快速而强大的免疫反应。为了深入了解巨噬细胞的可塑性以及控制其特定功能的关键调节蛋白网络，我们使用最新的基于等压标签的串联质量标签（TMT）标记和液相色谱-串联质谱（LC-MS/MS）技术，对小鼠原代粒细胞-巨噬细胞集落刺激因子（GM-CSF）和巨噬细胞集落刺激因子（M-CSF）培养的骨髓来源巨噬细胞（分别为GM-BMMs和M-BMMs）的蛋白质组和磷酸化蛋白质组进行了定量分析。引人注目的是，代谢过程成为这些巨噬细胞之间的主要差异。具体而言，GM-BMMs显示出参与糖酵解、甲羟戊酸途径和氮化合物生物合成的蛋白质显著富集。GM-BMMs糖酵解能力增强的这一证据在其促炎反应方面尤为重要，因为GM-BMMs在脂多糖刺激下细胞因子产量的增加取决于它们的急性糖酵解能力。相比之下，M-BMMs上调参与内吞作用的蛋白质，这与诸如清除细胞碎片等稳态功能的趋势相关。总之，我们的数据描述了一个蛋白质组网络，它是GM-BMMs促炎作用以及M-BMMs稳态功能的基础。
