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 failur e of transplanted livers. The aim of this study was to evaluate Kupffe r cell activity, leukocyte adhesion, and the effect of the calcium cha nnel blocker nisoldipine after rat liver transplantation by means of i n vivo fluorescence microscopy to further investigate the mechanism of graft failure. Inclusion of 1.4 muM nisoldipine to the University of Wisconsin cold storage solution (UW) did not improve sinusoidal perfus ion 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 Am diam of sinusoids; means +/-SE). Permanent as well as te mporary 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 liv er transplantation, respectively. Inclusion of the calcium channel blo cker 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 inc lusion of nisoldipine to UW (322 +/-32/MM2) . The results of this stud y demonstrate activation of Kupffer cells and increase of leukocyte ad hesion to the sinusoidal endothelial wall during reperfusion of transp lanted livers. A calcium-dependent release of mediators by Kupffer cel ls that promote leukocyte adhesion is suggested as an underlying mecha nism.