Impact of leukocyte-endothelial cell interaction in hepatic ischemia-reperfusion injury

Abstract

To clarify the in vivo relevance of leukocyte-endothelial cell interactions in the manifestation of hepatic ischemia-reperfusion (I/R) injury, we studied leukocyte flow behavior in sinusoids and postsinusoidal venules of postischemic hepatic tissue in rats using intravital microscopy. Reperfusion following either 20 min (n = 9) or 60 min (n = 9) of left hepatic lobar ischemia resulted in a significant increase of the number of stagnant leukocytes in sinusoids and adherent cells in postsinusoidal venules compared with sham-operated controls (n = 10). Transmission electron microscopy revealed the extravasation of leukocytes from both sinusoids (into the space of Disse) and postsinusoidal venules. In parallel, hepatic I/R was associated with increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and reduced bile flow. Linear regression estimates revealed significant (P < 0.01) correlations between serum ALT (r = 0.76) and AST (r = 0.65) activities, bile flow (r = -0.62), and the number of adherent leukocytes in postsinusoidal venules. In contrast, parameters of hepatocellular integrity and function did not directly correlate with the number of stagnant leukocytes in liver sinusoids. We conclude that hepatic I/R induces accumulation, adherence, and extravasation of leukocytes in both hepatic sinusoids and postsinusoidal venules. However, the adherence of leukocytes to the endothelial lining of venules, rather than of sinusoids, may determine the manifestation of hepatocellular damage and liver dysfunction.