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)定义淋巴细胞募集到小鼠皮肤中的时间过程和群体动力学，绘制淋巴细胞积累的地形图并表征相关微血管中的淋巴细胞和血浆流动2）将特定目标#1的目标扩展到小鼠肺和肠3）定义皮肤的形态结构特征，肠道和肺部炎症微循环4）确定炎症微循环中结构适应的功能后果。所提出的“微血液动力学”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”的血管结构适应性发展的调节。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，使炎症微循环的详细观察。第四个目标将通过使用高等数学来预测淋巴细胞迁移区域中的内皮壁剪切应力来实现。该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.