Mechanisms regulating adhesion-induced Weibel-Palade body exocytosis

粘附诱导 Weibel-Palade 小体胞吐作用的调节机制

• 批准号: 436191-2013
• 负责人: Patel, Kamala
• 金额: $ 2.62万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629180
• 关键词: Mechanisms; regulating; adhesion; induced; Weibel

The research program in my laboratory focuses on endothelial cells. Endothelial cells line the blood vessels and serve as gatekeepers, directing what molecules and cells can pass through into the tissue. In particular, endothelial cells regulate the movement of white blood cells during both immediate injury and during chronic disease. Endothelial cells are positioned between the fast flowing blood and the stationary tissue. As a result, they are very sensitive to changes in mechanical force. When white blood cells bind to endothelial cells, they rapidly decelerate, resulting in a large change in force at the point of contact. This change in force is sensed by the endothelial cells and translated into biochemical signals. This proposal examines how the mechanical force of white blood cell binding leads to changes in the endothelial cells that results in the release of intracellular storage granules called Weibel-Palade bodies. The contents of these granules affect blood clotting and edema, and can amplify the recruitment of white blood cells in chronic disease. We will culture cells from human umbilical veins to recreate blood vessels and obtain white blood cells from healthy volunteers. We will deliver fluorescently labeled proteins into the endothelial cells to enable tracking of Weibel-Palade bodies in living cells. We then assemble a flow chamber that mimics the conditions found in the blood stream. Using this system we will examine mechanisms that regulate the release of Weibel-Palade bodies in real-time during white blood cell binding in a model of chronic disease.

我实验室的研究方向是内皮细胞。内皮细胞排列在血管上，充当看门人的角色，指导哪些分子和细胞可以进入组织。特别是，内皮细胞在即时损伤和慢性疾病期间调节白细胞的运动。内皮细胞位于快速流动的血液和静止的组织之间。因此，它们对机械力的变化非常敏感。当白细胞与内皮细胞结合时，它们会迅速减速，导致接触点的作用力发生很大变化。这种力量的变化被内皮细胞感知并转化为生化信号。该提案研究了白细胞结合的机械力如何导致内皮细胞的变化，从而导致细胞内储存颗粒（称为Weibel-Palade小体）的释放。这些颗粒的内容物影响血液凝固和水肿，并能在慢性疾病中增加白细胞的募集。我们将培养取自人类脐静脉的细胞来再造血管，并从健康志愿者身上获得白细胞。我们将把荧光标记的蛋白质传递到内皮细胞中，以便在活细胞中跟踪韦贝尔-帕拉德体。然后我们组装一个模拟血液流动条件的流动室。使用该系统，我们将研究在慢性疾病模型中白细胞结合过程中实时调节韦贝尔-帕拉德体释放的机制。