Adhesion molecules and CXC chemokines in endotoxin-induced liver injury.
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.
Ohira
Hiromasa
H
Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
Abe
Kazumichi
K
Yokokawa
Junko
J
Takiguchi
Junko
J
Rai
Tsuyoshi
T
Shishido
Shoichiro
S
Sato
Yukio
Y
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
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