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: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=574308
• 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.

我实验室的研究项目集中在内皮细胞上。 内皮细胞排列在血管中，充当守门人，指导分子和细胞进入组织。 特别地，内皮细胞在即刻损伤期间和慢性疾病期间调节白色血细胞的运动。 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。 当白色血细胞与内皮细胞结合时，它们迅速减速，导致接触点的力发生很大变化。 这种力的变化被内皮细胞感知并转化为生化信号。 该提案研究了白色血细胞结合的机械力如何导致内皮细胞的变化，从而导致称为韦伯-帕拉德体的细胞内储存颗粒的释放。 这些颗粒的内容物影响血液凝固和水肿，并能放大慢性疾病中白色血细胞的募集。 我们将从人类脐静脉中培养细胞来重建血管，并从健康志愿者中获得白色血细胞。我们将把荧光标记的蛋白质递送到内皮细胞中，以使活细胞中的韦伯-帕拉德体能够被追踪。然后，我们组装一个流动室，模仿血液中的条件。 使用这个系统，我们将研究机制，调节释放的韦伯-帕拉德机构在实时白色血细胞结合在慢性疾病模型。