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
Statistics from Altmetric.com
Published Online First 17 November 2006
Funding: Supported in part by NIH Grant HL47078 and HL75426.
Competing interests: None.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.