Das Debjani, Aradhya Rajaguru, Ashoka D, Inamdar Maneesha
Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur PO, Bangalore 560064, India.
Exp Cell Res. 2008 May 1;314(8):1804-10. doi: 10.1016/j.yexcr.2008.02.009. Epub 2008 Feb 29.
The vertebrate reticuloendothelial system (RES) functions to remove potentially damaging macromolecules, such as excess hormones, immune-peptides and -complexes, bacterial-endotoxins, microorganisms and tumor cells. Insect hemocytes and nephrocytes - which include pericardial cells (PCs) and garland cells - are thought to be functionally equivalent to the RES. Although the ability of both vertebrate scavenger endothelial cells (SECs) and PCs to sequester colloidal and soluble macromolecules has been demonstrated the molecular mechanism of this function remains to be investigated. We report here the functional characterization of Drosophila larval PCs with important insights into their cellular uptake pathways. We demonstrate the nephrocyte function of PCs in live animals. We also develop and use live-cell assays to show that PCs take up soluble macromolecules in a Dynamin-dependent manner and colloids by a Dynamin-independent pathway. We had earlier identified Drosophila rudhira (Drudh) as a specific marker for PCs. Using RNAi mediated knock-down we show that Drudh regulates macropinocytic uptake in PCs. Our study establishes important functions for Drosophila PCs, describes methods to identify and study them, provides a genetic handle for further investigation of their role in maintaining homeostasis and demonstrates that they perform key subsets of the roles played by the vertebrate RES.
脊椎动物的网状内皮系统(RES)的功能是清除潜在有害的大分子,如过量的激素、免疫肽和免疫复合物、细菌内毒素、微生物及肿瘤细胞。昆虫血细胞和肾细胞(包括心包细胞(PCs)和花环细胞)在功能上被认为等同于RES。尽管脊椎动物的清道夫内皮细胞(SECs)和PCs摄取胶体和可溶性大分子的能力已得到证实,但该功能的分子机制仍有待研究。我们在此报告果蝇幼虫PCs的功能特性,并对其细胞摄取途径有重要见解。我们在活体动物中证明了PCs的肾细胞功能。我们还开发并使用活细胞检测方法,表明PCs以依赖发动蛋白的方式摄取可溶性大分子,并通过不依赖发动蛋白的途径摄取胶体。我们之前已将果蝇rudhira(Drudh)鉴定为PCs的特异性标志物。通过RNA干扰介导的敲低,我们表明Drudh调节PCs中的巨胞饮摄取。我们的研究确立了果蝇PCs的重要功能,描述了鉴定和研究它们的方法,为进一步研究它们在维持体内平衡中的作用提供了遗传手段,并证明它们执行脊椎动物RES所发挥作用的关键子集。