Macrophage activation and leukocyte adhesion after liver transplantation.
Reperfusion injury involving oxygen radicals, leukocyte adhesion, and Kupffer cell activation has been suggested to contribute to the failure of transplanted livers. The aim of this study was to evaluate Kupffer cell activity, leukocyte adhesion, and the effect of the calcium channel blocker nisoldipine after rat liver transplantation by means of in vivo fluorescence microscopy to further investigate the mechanism of graft failure. Inclusion of 1.4 microM nisoldipine to the University of Wisconsin cold storage solution (UW) did not improve sinusoidal perfusion and vasoconstriction after transplantation compared with UW alone (82.7 +/- 1.0% vs. 79.2 +/- 1.7% perfused sinusoids; 7.3 +/- 0.1 vs. 8.0 +/- 0.2 microns diam of sinusoids; means +/- SE). Permanent as well as temporary adhesion of leukocytes rose from 9.4 +/- 0.8 and 10.2 +/- 0.5% in sham-operated controls to 19.1 +/- 2.2 and 19.2 +/- 0.5% after liver transplantation, respectively. Inclusion of the calcium channel blocker reduced permanent (9.1 +/- 0.8%; P < 0.05) and temporary adherent leukocytes (11.3 +/- 1.0%; P < 0.05). Phagocytosis of latex beads by Kupffer cells or other phagocytic cells as a function of activity rose after transplantation (e.g., periportal area: 509 +/- 44/mm2) compared with controls (316 +/- 22/mm2). This was significantly reduced by inclusion of nisoldipine to UW (322 +/- 32/mm2). The results of this study demonstrate activation of Kupffer cells and increase of leukocyte adhesion to the sinusoidal endothelial wall during reperfusion of transplanted livers. A calcium-dependent release of mediators by Kupffer cells that promote leukocyte adhesion is suggested as an underlying mechanism.
Marzi
I
I
Department of Surgery, University of Saarland, Homburg/Saar, Germany.
Walcher
F
F
Bühren
V
V
D000818:Animals; D002448:Cell Adhesion; D005260:Female; D007728:Kupffer Cells / Q000502:physiology; D007840:Latex; D007962:Leukocytes / Q000502:physiology*; D008102:Liver Circulation / Q000187:drug effects; D016031:Liver Transplantation; D008264:Macrophages / Q000502:physiology*; D008863:Microspheres; D015737:Nisoldipine / Q000494:pharmacology; D010587:Phagocytosis; D011184:Postoperative Period; D051381:Rats; D011917:Rats, Inbred Lew
D007840:Latex; D015737:Nisoldipine