Nonaka Saori, Hori Aki, Nakanishi Yoshinobu, Kuraishi Takayuki
Graduate School of Medical Sciences, Kanazawa University.
Graduate School of Medical Sciences, Kanazawa University;
J Vis Exp. 2017 Aug 3(126):56352. doi: 10.3791/56352.
The molecular mechanisms underlying the phagocytosis of apoptotic cells need to be elucidated in more detail because of its role in immune and inflammatory intractable diseases. We herein developed an experimental method to investigate phagocytosis quantitatively using the fruit fly Drosophila, in which the gene network controlling engulfment reactions is evolutionally conserved from mammals. In order to accurately detect and count engulfing and un-engulfing phagocytes using whole animals, Drosophila embryos were homogenized to obtain dispersed cells including phagocytes and apoptotic cells. The use of dispersed embryonic cells enables us to measure in vivo phagocytosis levels as if we performed an in vitro phagocytosis assay in which it is possible to observe all phagocytes and apoptotic cells in whole embryos and precisely quantify the level of phagocytosis. We confirmed that this method reproduces those of previous studies that identified the genes required for the phagocytosis of apoptotic cells. This method allows the engulfment of dead cells to be analyzed, and when combined with the powerful genetics of Drosophila, will reveal the complex phagocytic reactions comprised of the migration, recognition, engulfment, and degradation of apoptotic cells by phagocytes.
由于凋亡细胞吞噬作用在免疫和炎症难治性疾病中的作用,其潜在的分子机制需要更详细地阐明。我们在此开发了一种使用果蝇来定量研究吞噬作用的实验方法,其中控制吞噬反应的基因网络在进化上与哺乳动物保守。为了使用完整动物准确检测和计数吞噬和未吞噬的吞噬细胞,将果蝇胚胎匀浆以获得包括吞噬细胞和凋亡细胞的分散细胞。使用分散的胚胎细胞使我们能够测量体内吞噬作用水平,就好像我们进行了体外吞噬作用测定一样,在体外吞噬作用测定中可以观察整个胚胎中的所有吞噬细胞和凋亡细胞,并精确量化吞噬作用水平。我们证实,该方法重现了先前鉴定凋亡细胞吞噬所需基因的研究方法。该方法允许分析死细胞的吞噬情况,并且当与果蝇强大的遗传学相结合时,将揭示由吞噬细胞对凋亡细胞的迁移、识别、吞噬和降解组成的复杂吞噬反应。