Vascular Adaptations in Lymphocyte Transmigration

描述（由申请人提供）：拟议的研究项目有4个具体目标。1)确定淋巴细胞募集到小鼠皮肤的时间过程和群体动态，绘制淋巴细胞积累的地形图，并表征相关微血管中淋巴细胞和血浆的流动特征2)将特异性目标# 1的目标扩展到小鼠肺和肠道3)确定皮肤、肠道和肺部炎症微循环的形态结构特征4)确定炎症微循环结构适应的功能后果。提出的“微血流动力学”假说认为，淋巴细胞的迁移将受到微循环中称为“微血管扩张”的血管结构适应的发展所调节。第一个和第二个目标将通过小鼠组织H&E组织学、免疫组织化学、荧光活体显微镜和3D组织切片的抗原致敏/激发来实现。第三个目标将集中在使用3D组织切片和腐蚀铸造/扫描电子显微镜对炎症微循环进行详细观察。第四个目标将通过使用高等数学来预测内皮壁剪切应力在淋巴细胞迁移的领域。本研究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.