Hanington Patrick C, Tam Jonathan, Katzenback Barbara A, Hitchen Steven J, Barreda Daniel R, Belosevic Miodrag
Department of Biological Sciences, University of Alberta, Alberta, Canada.
Dev Comp Immunol. 2009 Apr;33(4):411-29. doi: 10.1016/j.dci.2008.11.004. Epub 2008 Dec 6.
The innate immune responses of early vertebrates, such as bony fishes, play a central role in host defence against infectious diseases and one of the most important effector cells of innate immunity are macrophages. In order for macrophages to be effective in host defence they must be present at all times in the tissues of their host and importantly, the host must be capable of rapidly increasing macrophage numbers during times of need. Hematopoiesis is a process of formation and development of mature blood cells, including macrophages. Hematopoiesis is controlled by soluble factors known as cytokines, that influence changes in transcription factors within the target cells, resulting in cell fate changes and the final development of specific effector cells. The processes involved in macrophage development have been largely derived from mammalian model organisms. However, recent advancements have been made in the understanding of macrophage development in bony fish, a group of organisms that rely heavily on their innate immune defences. Our understanding of the growth factors involved in teleost macrophage development, as well as the receptors and regulatory mechanisms in place to control them has increased substantially. Furthermore, model organisms such as the zebrafish have emerged as important instruments in furthering our understanding of the transcriptional control of cell development in fish as well as in mammals. This review highlights the recent advancements in our understanding of teleost macrophage development. We focused on the growth factors identified to be important in the regulation of macrophage development from a progenitor cell into a functional macrophage and discuss the important transcription factors that have been identified to function in teleost hematopoiesis. We also describe the findings of in vivo studies that have reinforced observations made in vitro and have greatly improved the relevance and importance of using teleost fish as model organisms for studying developmental processes.
早期脊椎动物,如硬骨鱼的先天免疫反应在宿主抵御传染病中起着核心作用,而先天免疫中最重要的效应细胞之一是巨噬细胞。为了使巨噬细胞在宿主防御中发挥有效作用,它们必须始终存在于宿主组织中,重要的是,宿主必须能够在需要时迅速增加巨噬细胞数量。造血是包括巨噬细胞在内的成熟血细胞形成和发育的过程。造血受称为细胞因子的可溶性因子控制,这些因子影响靶细胞内转录因子的变化,导致细胞命运改变和特定效应细胞的最终发育。巨噬细胞发育所涉及的过程在很大程度上源自哺乳动物模式生物。然而,最近在硬骨鱼巨噬细胞发育的理解方面取得了进展,硬骨鱼是一类严重依赖其先天免疫防御的生物。我们对参与硬骨鱼巨噬细胞发育的生长因子以及控制它们的受体和调节机制的理解有了大幅增加。此外,斑马鱼等模式生物已成为推进我们对鱼类以及哺乳动物细胞发育转录控制理解的重要工具。本综述强调了我们在硬骨鱼巨噬细胞发育理解方面的最新进展。我们重点关注已确定在将祖细胞发育为功能性巨噬细胞的过程中对巨噬细胞发育调节重要的生长因子,并讨论已确定在硬骨鱼造血中起作用的重要转录因子。我们还描述了体内研究的结果,这些结果强化了体外观察结果,并大大提高了使用硬骨鱼作为研究发育过程模式生物的相关性和重要性。