Vascular Adaptations in Lymphocyte Transmigration

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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.