Centre for Inflammation Research, University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Centre for Inflammation Research, University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Cell Rep. 2020 May 26;31(8):107692. doi: 10.1016/j.celrep.2020.107692.
Macrophages must not only be responsive to an array of different stimuli, such as infection and cellular damage, but also perform phagocytosis within the diverse and complex tissue environments found in vivo. This requires a high degree of morphological and therefore cytoskeletal plasticity. Here, we use the exceptional genetics and in vivo imaging of Drosophila embryos to study macrophage phagocytic versatility during apoptotic corpse clearance. We find that macrophage phagocytosis is highly robust, arising from their possession of two distinct modes of engulfment that utilize exclusive suites of actin-regulatory proteins. "Lamellipodial phagocytosis" is Arp2/3-complex-dependent and allows cells to migrate toward and envelop apoptotic corpses. Alternatively, Diaphanous and Ena drive filopodial phagocytosis to reach out and draw in debris. Macrophages switch to "filopodial phagocytosis" to overcome spatial constraint, providing the robust plasticity necessary to ensure that whatever obstacle they encounter in vivo, they fulfil their critical clearance function.
巨噬细胞不仅必须对感染和细胞损伤等一系列不同的刺激做出反应，还必须在体内发现的多样化和复杂的组织环境中进行吞噬作用。这需要高度的形态和细胞骨架可塑性。在这里，我们利用果蝇胚胎的特殊遗传学和体内成像技术，研究巨噬细胞在清除凋亡细胞时的吞噬多功能性。我们发现巨噬细胞的吞噬作用非常强大，这源于它们拥有两种不同的吞噬方式，这两种方式利用了独特的肌动蛋白调节蛋白套件。“片状伪足吞噬”依赖于 Arp2/3 复合物，使细胞能够向凋亡细胞迁移并包裹它们。另一方面，Dia 和 Ena 驱动丝状伪足吞噬作用，伸出并摄取碎片。巨噬细胞转而进行“丝状伪足吞噬”以克服空间限制，从而提供必要的强大可塑性，以确保它们在体内遇到任何障碍物时，都能完成其关键的清除功能。
