Department of Biochemistry and Department of Physiology and Pharmacology, University of Bristol, BS8 1TD Bristol, UK.
Curr Biol. 2010 Mar 9;20(5):464-70. doi: 10.1016/j.cub.2010.01.047. Epub 2010 Feb 25.
The function of immune cells is critically dependent on their capacity to respond to a complex series of navigational cues that enable them to home to various organ sites in the body or to respond to inflammatory cues such as those released at sites of tissue damage. From early embryonic stages, immune cells are faced with a barrage of signals that will not all be directing the cell to do the same thing. Here we use the Drosophila embryo to investigate how hemocytes (Drosophila macrophages), are able to prioritize key guidance signals and ignore others so that they are not pulled every which way. We identify the immediate wound attractant signal as H(2)O(2) and investigate how Drosophila macrophages respond to competing guidance cues-those emanating from a wound-versus standard developmental guidance cues, as well as those signals drawing cells toward neighboring dying cells. We reveal a hierarchy of responsiveness to attractant cues that varies over time and we identify why there is a wound refractile period early in embryonic development when macrophages cannot be distracted from their developmental migratory pathway to a site of tissue damage.
免疫细胞的功能严重依赖于它们响应一系列复杂导航线索的能力，这些线索使它们能够归巢到体内的各种器官部位，或响应炎症线索，如在组织损伤部位释放的那些线索。从早期胚胎阶段开始，免疫细胞就面临着一连串的信号，而并非所有信号都能指示细胞做同样的事情。在这里，我们使用果蝇胚胎来研究血细胞（果蝇巨噬细胞）如何能够优先考虑关键的指导信号并忽略其他信号，从而不会被各种信号拉向不同的方向。我们确定了即时的伤口吸引信号是 H(2)O(2)，并研究了果蝇巨噬细胞如何响应竞争的指导线索——那些来自伤口的与标准发育指导线索，以及那些吸引细胞向邻近死亡细胞的信号。我们揭示了对吸引线索的响应存在一个随时间变化的层次结构，并确定了为什么在胚胎发育的早期会有一个伤口反射期，此时巨噬细胞不能从其发育性迁移途径转移到组织损伤部位。
