Evidence shows that leukocyte recruitment into inflamed liver sinusoids does not require
selectins, with one notable exception:
ischemia-reperfusion (I/R). We used intravital microscopy to directly visualize the liver microcirculation during I/R and localized
endotoxemia (liver superfused with
lipopolysaccharide). General anti-
selectin therapy (
fucoidan) or anti-adhesion
therapy with an
antithrombin inhibitor (
hirudin) was also used. Many neutrophils rolled and adhered in postsinusoidal vessels and sequestered in the sinusoids during I/R and local
endotoxin superfusion. Although
fucoidan blocked rolling in both forms of
inflammation, leukocyte recruitment into sinusoids was only blocked in I/R. Adhesion was also inhibited in postischemic sinusoids with a second anti-adhesive agent (
hirudin). Because liver I/R inevitably induces
ischemia upstream in the intestine, anti-
selectin therapy may prevent intestinal injury, which could prevent downstream liver
inflammation. To test this hypothesis, we completely removed the intestine and rerouted blood flow from the superior mesenteric artery to the superior mesenteric vein. I/R was induced in the liver microcirculation, and many leukocytes rolled and adhered in postsinusoidal venules and adhered in sinusoids. Although
fucoidan significantly reduced the rolling in postsinusoidal vessels, adhesion persisted in the sinusoids. Our data suggest that anti-adhesion
therapy is effective in liver I/R in the sinusoids and postsinusoidal venules, perhaps in part due to its beneficial effect on the intestine.