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Structural Adaptations in the Murine Colon Microcirculation Associated with Hapten-induced Inflammation
  1. Dino J Ravnic (dravnic{at}
  1. Brigham & Women's Hospital, United States
    1. Moritz A. Konerding (konerdin{at}
    1. Johannes Gutenberg University, Germany
      1. Akira Tsuda (atsuda{at}
      1. Harvard School of Public Health, United States
        1. Juan P. Pratt (jppratt{at}
        1. Brigham & Women's Hospital, United States
          1. Harold Huss (hhuss{at}
          1. Brigham & Women's Hospital, United States
            1. Tanya Wollonschenk (wollosch{at}
            1. Johannes Gutenberg University, Germany
              1. Steven J. Mentzer (smentzer{at}
              1. Brigham & Women's Hospital, United States


                Objectives: Blood flowing across the vascular endothelium creates wall shear stress, dependent on flow velocity and vessel geometry, that tends to disrupt lymphocyte-endothelial cell adhesion. To identify structural adaptations during acute colitis that may facilitate transmigration, we investigated the microcirculation in a murine model of acute colitis.

                Methods: In trinitrobenzenesulfonic acid (TNBS)- induced acute colitis, the infiltrating cells and colonic microcirculation was investigated by cellular topographic mapping as well as corrosion casting and 3- dimensional (3D) scanning electron microscopy. Colonic blood velocimetry was performed using intravital microscopy.

                Results: Clinical and histologic parameters suggested a peak inflammatory response at 96 hours (p<.001). The infiltrating cells were spatially related to the mucosal capillary plexus by 3-D topographic mapping (p<.001). In normal mice, corrosion casting and 3-D scanning electron microscopy (3D-SEM) demonstrated a polygonal mucosal plexus supplied by ascending arteries and descending veins. After TNBS stimulation, 3D-SEM demonstrated preserved branch angles (p=.52) and nominal vessel lengths (p=.93), but a significantly dilated mucosal capillary plexus (p<.001). Intravital microscopy of the mucosal plexus demonstrated a greater than 2-fold decrease in flow velocity (p<.001).

                Conclusions: The demonstrable slowing of flow velocity despite an increase in volumetric flow suggests that these microvascular adaptations create conditions suitable for leukocyte adhesion and transmigration.

                • colitis
                • leukocytes
                • microcirculation
                • scanning electron microscopy
                • velocimetry

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