Regulation and function of Duffy antigen receptor for chemokines (DARC) in primary endothelial cells

原代内皮细胞达菲抗原趋化因子受体 (DARC) 的调节和功能

• 批准号: RGPIN-2020-04299
• 负责人: Lee, Warren
• 金额: $ 3.06万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744136
• 关键词: Regulation; function; Duffy; antigen; receptor

The Duffy antigen receptor for chemokines (commonly abbreviated as DARC) is a molecule on cells that line blood vessels - known as endothelial cells. DARC exists in many species of mammals including humans, suggesting that it has an important function. However, what DARC does on endothelial cells is not known. One of the reasons why the function of DARC is not understood is because endothelial cells stop making DARC when they are grown in the lab. For some reason, DARC can only be detected on the endothelial cells of animals and not on endothelial cells grown on dishes in the lab. My lab discovered that letting endothelial cells on a dish be exposed to blood caused the endothelial cells to start making DARC again. This lucky observation may allow us to study what DARC does in endothelial cells. In this grant application, we are proposing to find out how human blood causes the endothelial cells to make DARC. What component of the blood is having this effect? Next, we will figure out why DARC goes away from the cells in the absence of blood. Lastly, we will figure out the purpose of DARC in endothelial cells. We believe that DARC is probably governing the immune system because white blood cells interact with endothelial cells when they respond to an infection. Our study is important because understanding what DARC does and how DARC production is governed will increase our understanding of the immune system.

趋化因子的达菲抗原受体（通常缩写为DARC）是血管内皮细胞上的一种分子。DARC存在于包括人类在内的许多哺乳动物中，这表明它具有重要的功能。然而，DARC对内皮细胞的作用尚不清楚。DARC的功能不被理解的原因之一是因为内皮细胞在实验室中生长时停止制造DARC。由于某种原因，DARC只能在动物的内皮细胞上检测到，而不能在实验室培养皿上生长的内皮细胞上检测到。我的实验室发现，让培养皿上的内皮细胞接触血液，会导致内皮细胞再次开始制造DARC。这一幸运的观察可能使我们能够研究DARC在内皮细胞中的作用。在这项拨款申请中，我们打算找出人类血液如何导致内皮细胞产生DARC。血液中的什么成分有这种作用？接下来，我们将弄清楚为什么DARC在没有血液的情况下离开细胞。最后，我们将弄清楚DARC在内皮细胞中的作用。我们认为DARC可能控制免疫系统，因为当白色血细胞对感染作出反应时，它们与内皮细胞相互作用。我们的研究很重要，因为了解DARC的作用以及DARC的产生是如何控制的，将增加我们对免疫系统的理解。