Vascular Adaptations in Lymphocyte Transmigration

描述(申请者提供)：本研究项目有4个具体目标。1)定义淋巴细胞重新聚集到小鼠皮肤的时间进程和种群动态，绘制淋巴细胞聚集的拓扑图，并描述相关微血管中的淋巴细胞和血浆流动2)将特定目标1的目标扩展到小鼠的肺和肠道3)定义皮肤、肠道和肺炎性微循环的形态结构特征4)确定炎症微循环中结构适应的功能后果。提出的“微血流动力学”假说认为，淋巴细胞的迁移将由微循环中血管结构适应性的发展来调节，称为“微血管扩张”。第一个和第二个目标将通过抗原敏化/挑战小鼠组织的H&E组织学、免疫组织化学、荧光活体显微镜和3D组织切片来实现。第三个目标将集中在使用3D组织切片和腐蚀铸型/扫描电子显微镜来详细观察炎症微循环。第四个目标将通过使用高级数学来预测淋巴细胞移行区域的内皮细胞壁切应力来实现。这一建议旨在阐明调节淋巴细胞迁移的基本机制。

DESCRIPTION (provided by applicant): The proposed research project has 4 specific aims. 1) Define the time course and population dynamics of lymphocyte recruitment into the murine skin, map the topography of lymphocyte accumulation and characterize lymphocyte and plasma flow in the associated microvessels 2) Extend the objectives of Specific Aim # 1 to the mouse lung and gut 3) Define the morphometric structural features of the skin, gut and lung inflammatory microcirculation 4) Identify the functional consequences of structural adaptations in the inflammatory microcirculation. The proposed "microhemodynamic" hypothesis is that lymphocyte transmigration will be regulated by the development of vascular structural adaptations in the microcirculation called "microangiectasias". The first and second aims will be accomplished through antigen sensitization/challenge of mouse tissues H&E histology, immunohistochemistry, fluorescence intravital microscopy and 3D tissue sections. The third aim will focus on the use of 3D tissue sections and corrosion casting/scanning electron microscopy to make detailed observations of the inflammatory microcirculation. The fourth aim will be achieved through the use of advanced mathematics to predict endothelial wall shear stress in the areas of lymphocyte transmigration. This proposal aims to elucidate a fundamental mechanism regulating lymphocyte transmigration.