title: Involvement of Kupffer cells in the interaction between neutrophils and sinusoidal endothelial cells in rats.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Morita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Daimon
authors.forename: Kyoko
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Kei
authors.initials: K
authors.lastname: Kashima
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology; D019446:Endotoxemia / Q000209:etiology / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D011336:Probability; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone