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Intestinal Disease Research Programme, Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
There is a
close relationship between inflammatory bowel disease (IBD) and various
hepatobiliary disorders. The objective of this study was to determine
whether hepatic leukocyte recruitment occurs in experimental colitis.
We used the murine model of colitis induced by
2,4-dinitrobenezenesulfonic acid (DNBS). Male C57Bl/6 mice received an
intrarectal injection of 4 mg DNBS in 100 µl 50% ethanol. Controls
received 100 µl 50% ethanol. The hepatic microcirculation was
examined at 3 and 14 days post-DNBS by intravital video microscopy.
Three days post-DNBS, when mice had developed acute colitis, there was
associated hepatic leukocyte recruitment. Within the postsinusoidal
venules there was a fourfold increase in the flux of rolling leukocytes
that was P-selectin dependent but not
4-integrin
dependent. There was also an increase in stationary leukocytes within
the sinusoids, although this was not associated with an increase in
serum alanine transaminase. By 14 days post-DNBS when macroscopic
evidence of colonic inflammation was resolved, rolling within the
postsinusoidal venules had returned to control levels. In this murine
model of colitis, we describe a link between acute colonic inflammation
and remote hepatic leukocyte recruitment that is P-selectin dependent.
Active IBD may lead to remote hepatic inflammation.
inflammatory bowel disease; intravital microscopy; microcirculation; P-selectin; integrins
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