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Structural adaptations in the murine colon microcirculation associated with hapten-induced inflammation
  1. Dino J Ravnic1,
  2. Moritz A Konerding2,
  3. Akira Tsuda3,
  4. Harold T Huss1,
  5. Tanja Wolloscheck2,
  6. Juan P Pratt1,
  7. Steven J Mentzer1
  1. 1Laboratory of Immunophysiology, Brigham & Women’s Hospital, Boston, Massachusetts, USA
  2. 2Department of Anatomy, Johannes Gutenberg University, Mainz, Germany
  3. 3Department of Physiology, Harvard School of Public Health, Boston, Massachusetts, USA
  1. Correspondence to:
    Dr S J Mentzer
    Room 259, Brigham & Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA; smentzer{at}partners.org

Abstract

Background: Blood flowing across the vascular endothelium creates wall shear stress, dependent on velocity of flow and vessel geometry, that tends to disrupt lymphocyte–endothelial cell adhesion.

Objective: The microcirculation in a murine model of acute colitis was investigated to identify structural adaptations during acute colitis that may facilitate transmigration.

Methods: In 2,4,6-trinitrobenzenesulphonic acid-induced acute colitis, the infiltrating cells and colonic microcirculation was investigated by cellular topographic mapping, corrosion casting and three-dimensional scanning electron microscopy (SEM). Colonic blood velocimetry was performed using intravital microscopy.

Results: Clinical and histological parameters suggested a peak inflammatory response at 96 h (p<0.001). The infiltrating cells were spatially related to the mucosal capillary plexus by three-dimensional topographic mapping (p<0.001). In normal mice, corrosion casting and three-dimensional SEM showed a polygonal mucosal plexus supplied by ascending arteries and descending veins. After 2,4,6-trinitrobenzenesulphonic acid stimulation, three-dimensional SEM showed preserved branch angles (p = 0.52) and nominal vessel lengths (p = 0.93), but a significantly dilated mucosal capillary plexus (p<0.001). Intravital microscopy of the mucosal plexus showed a greater than twofold decrease in the velocity of flow (p<0.001).

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

  • CFSE, 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester
  • PBS, phosphate buffered saline
  • SEM, scanning electron microscopy
  • TNBS, 2,4,6-trinitrobenzenesulphonic acid
  • TNCB, 2,4,6-trinitrochlorobenzene

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Footnotes

  • Published Online First 17 November 2006

  • Funding: Supported in part by NIH Grant HL47078 and HL75426.

  • Competing interests: None.

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