REGULATION OF MOTILITY AND TRANSCRIPTION IN INFLAMMATION

细胞运动是炎症反应的重要组成部分。在内皮细胞层上的循环白细胞停止后，白细胞移动到渗出部位，经历渗出，最后迁移到感染部位。在这些过程中，由一类细胞因子、可溶性趋化因子或其他与内皮细胞表面结合的分子介导的趋化梯度将招募和引导各种类型的白细胞。我们的总体目标是研究炎症过程中细胞运动的调节与转录是如何协调的。这一建议的一般假设是，参与炎症反应的细胞的运动与编码各种细胞因子的某些基因的转录是耦合的。这被认为是通过多种因素发生的，包括细胞内钙和Rho家族的小GTP结合蛋白，调节细胞的组织、动力学和生物力学特性，进而调节它们的运动行为。这项工作的一个相关方面将解决如何通过转录调节将细胞运动与基因表达联系起来。然后，我们将研究白细胞通过内皮细胞外渗过程中运动事件的调节。这项提议的一个新方面是，大多数这些研究将使用成像和新的光诱导技术在单个细胞上进行。

Cell movement is an essential component of the inflammatory response. After arrest of circulating leukocytes on the endothelial layer, leukocytes move to the site of extravasation, undergo diapedesis, and finally migrate to sites of infection. In these processes, various types of leukocytes will be recruited and guided by chemotactic gradients mediated by a class of cytokines, the soluble chemokines, or by other molecules bound to the endothelial cell surface. Our overall objective is to investigate how the regulation of cell motility is coordinated with transcription during inflammation. The general hypothesis of this proposal is that the movement of cells participating in the inflammatory response is coupled to the transcription of certain genes that code for various cytokines. This is thought to occur via factors, including intracellular calcium and the Rho family of small GTP-binding proteins, regulating the organization, dynamics and biomechanical properties of cells and, in turn, their motile behavior. A related aspect of this work will address how cell locomotion is linked to gene expression via transcriptional regulation. We will then study the regulation of motile events in the process of leukocyte extravasation through the endothelium. A novel aspect of this proposal is that most of these studies will be conducted on individual cells using imaging and new photomanipulative techniques.