title: Adhesion molecules and CXC chemokines in endotoxin-induced liver injury.
abstract: Interactions between leukocytes and sinusoidal endothelial cells are known to be involved in the pathogenesis of acute liver injury. Various adhesion molecules and chemokines play key roles in these cell-to-cell interactions, and the expression of these adhesion molecules and the production of chemokines are regulated by inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma). We have shown that the expression of intercellular adhesion molecule-1 (ICAM-1) on cultured rat sinusoidal endothelial cells stimulated with TNF-alpha increases in a dose-dependent manner. The number of neutrophils that adhered to sinusoidal endothelial cells pretreated with TNF-alpha also increased in a dose-dependent manner and significantly decreased upon incubation with an anti-ICAM-1 antibody. In endotoxin-induced rat liver injury, the number of neutrophils infiltrating the sinusoids increased after serum TNF-alpha, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) reached their peak levels. In addition, the level of ICAM-1 expression on sinusoidal endothelial cells greatly increased from 8 h after exposure to endotoxin, and these cells were adhered to neutrophils that expressed both LFA-1 and Mac-1. Moreover, lipo-prostaglandin E1 (PGE1) reduced the extent of liver injury, and also reduced the number of neutrophils that infiltrated the liver, was reduced the production of MIP-2 and CINC, but not that of TNF-alpha, in rats injected with endotoxin.
authors: Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors: Hiromasa
authors: H
authors: Ohira
authors: Kazumichi
authors: K
authors: Abe
authors: Junko
authors: J
authors: Yokokawa
authors: Junko
authors: J
authors: Takiguchi
authors: Tsuyoshi
authors: T
authors: Rai
authors: Shoichiro
authors: S
authors: Shishido
authors: Yukio
authors: Y
authors: Sato
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D054426:Chemokine CXCL2; D019743:Chemokines, CXC / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology; D004731:Endotoxins / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D015846:Monokines / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513296:Cxcl2 protein, rat; D004731:Endotoxins; D036341:Intercellular Signaling Peptides and Proteins; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000527:Alprostadil