Namgaladze Dmitry, Brüne Bernhard, Weigert Andreas
Goethe University Frankfurt, Faculty of Medicine, Institute of Biochemistry I, Frankfurt, Germany.
Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt, Germany.
Adv Exp Med Biol. 2025;1481:91-119. doi: 10.1007/978-3-031-92785-0_4.
Every day billions of cells are removed in the human body by apoptosis. These apoptotic cells need to be rapidly and safely removed in order to avoid inflammation. This is ensured by a process called efferocytosis, where professional phagocytes such as macrophages take up apoptotic cells. Efferocytosis not only ensures the safe removal of cellular debris but also endows phagocytes with the capacity to actively contribute to the resolution of inflammation by altering their phenotype. Therefore, actively promoting efferocytosis may contribute to the resolution of auto-inflammatory disease conditions. While the initial steps of the recognition of dying cells by macrophages are well investigated, it is less clear what happens to the ingested material inside the phagocyte and how it influences their pro-resolving properties. In this chapter, we therefore briefly discuss the impact of efferocytosis during inflammation. We focus on the metabolic challenge macrophages face when removing multiple dying cells, e.g., during inflammation, and how the knowledge resulting from understanding the molecular programs that promote corpse digestion might be used in the future to combat inflammatory diseases in humans.
在人体中,每天有数十亿细胞通过细胞凋亡被清除。这些凋亡细胞需要被迅速且安全地清除,以避免炎症反应。这通过一个称为胞葬作用的过程得以确保,在此过程中,诸如巨噬细胞等专业吞噬细胞会摄取凋亡细胞。胞葬作用不仅确保了细胞碎片的安全清除,还赋予吞噬细胞通过改变其表型来积极促进炎症消退的能力。因此,积极促进胞葬作用可能有助于自身炎症性疾病状态的消退。虽然巨噬细胞识别垂死细胞的初始步骤已得到充分研究,但吞噬细胞内摄入物质会发生什么以及它如何影响巨噬细胞的促消退特性尚不清楚。因此,在本章中,我们将简要讨论胞葬作用在炎症过程中的影响。我们关注巨噬细胞在清除多个垂死细胞时(例如在炎症期间)所面临的代谢挑战,以及理解促进尸体消化的分子程序所产生的知识在未来如何用于对抗人类炎症性疾病。