Involvement of Kupffer cells in the interaction between neutrophils and sinusoidal endothelial cells in rats. Shock 18(2):152-157, 2002.

During endotoxic liver injury, large numbers of neutrophils infiltrate the liver, and serum levels of tumor necrosis factor-alpha (TNF-alpha) become elevated. The object of this study was to assess the roles of TNF-alpha secreted by Kupffer cells in the interaction between neutrophils and sinusoidal endothelial cells (SECs). Rat neutrophils were perfused onto SECs that were stimulated with either TNF-alpha or supernatant from lipopolysaccharide (LPS)-stimulated Kupffer cells using an in vitro flow system. Numbers of adhered or migrated neutrophils were counted, and the effect of an antibody against intercellular adhesion molecule-1 (ICAM-1) was studied. Compared with controls (200 +/- 21 cells/mm2), neutrophil adhesion to SECs was significantly increased by both TNF-alpha (342 +/- 26 cells/mm2; P < 0.05) and LPS-stimulated Kupffer cell supernatant (331 +/- 29 cells/mm2; P < 0.05). Anti-ICAM-1 significantly inhibited neutrophil adhesion (139 +/- 10 cells/mm2; P < 0.05) and decreased the migration rate of neutrophils on SECs treated with LPS-stimulated Kupffer cell supernatant (P < 0.05). LPS-stimulated Kupffer cells secreted TNF-alpha in an LPS dose-dependent manner, and they significantly enhanced ICAM-1 expression on SECs (P < 0.05 vs. control). In addition, dexamethasone suppressed TNF-alpha production by LPS-stimulated Kupffer cells and decreased ICAM-1 expression and neutrophil adhesion on SECs. These findings suggest that Kupffer cells are involved in neutrophil adhesion and migration in hepatic sinusoids via TNF-alpha production and induction of ICAM-1 expression on SECs during liver injury associated with endotoxemia.