Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, UK.
Cell Death Differ. 2013 May;20(5):709-20. doi: 10.1038/cdd.2012.166. Epub 2013 Jan 18.
In vitro studies have shown that SCAR/WAVE activates the Arp2/3 complex to generate actin filaments, which in many cell types are organised into lamellipodia that are thought to have an important role in cell migration. Here we demonstrate that SCAR is utilised by Drosophila macrophages to drive their developmental and inflammatory migrations and that it is regulated via the Hem/Kette/Nap1-containing SCAR/WAVE complex. SCAR is also important in protecting against bacterial pathogens and in wound repair as SCAR mutant embryos succumb more readily to both sterile and infected wounds. However, in addition to driving the formation of lamellipodia in macrophages, SCAR is required cell autonomously for the correct processing of phagocytosed apoptotic corpses by these professional phagocytes. Removal of this phagocytic burden by preventing apoptosis rescues macrophage lamellipodia formation and partially restores motility. Our results show that efficient processing of phagosomes is critical for effective macrophage migration in vivo. These findings have important implications for the resolution of macrophages from chronic wounds and the behaviour of those associated with tumours, because phagocytosis of debris may serve to prolong the presence of these cells at these sites of pathology.
体外研究表明，SCAR/WAVE 激活 Arp2/3 复合物生成肌动蛋白丝，在许多细胞类型中，肌动蛋白丝组装成片状伪足，被认为在细胞迁移中起着重要作用。在这里，我们证明 SCAR 被果蝇巨噬细胞用于驱动其发育和炎症迁移，并且它通过 Hem/Kette/Nap1 包含的 SCAR/WAVE 复合物进行调节。SCAR 对于抵抗细菌病原体和伤口修复也很重要，因为 SCAR 突变体胚胎更容易受到无菌和感染伤口的影响。然而，除了在巨噬细胞中驱动片状伪足的形成之外，SCAR 还需要细胞自主地正确处理这些专业吞噬细胞吞噬的凋亡细胞。通过阻止细胞凋亡来消除这种吞噬负担，可以挽救巨噬细胞的片状伪足形成，并部分恢复运动性。我们的研究结果表明，有效的吞噬体处理对于体内巨噬细胞的有效迁移至关重要。这些发现对于慢性伤口中巨噬细胞的清除以及与肿瘤相关的巨噬细胞的行为具有重要意义，因为吞噬碎片可能会延长这些细胞在这些病理部位的存在时间。
