Chronic Ethanol Consumption Enhances Endotoxin Induced Hepatic Sinusoidal Leukocyte Adhesion

Ohki, Eiji; Kato, Suzuka; Horie, Yoshinori; Mizukami, Takeshi; Tamai, Hironao; Yokoyama, Hirokazu; Ito, Daisuke; Fukuda, Masahiko; Suzuki, Hidekazu; Kurose, Iwao; Ishii, Hiromasa

doi:10.1111/j.1530-0277.1996.tb01171.x

Cited by 11 publications

(27 citation statements)

References 12 publications

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“…It is well accepted that severe stages of ALD are associated with microcirculation dysfunction (20). In a rat model of ALD, chronic alcohol consumption led to hepatic microcirculation disruption characterized by decreased red blood cell velocity and sinusoidal shutdown (21). This study suggested that increased leukocyte adhesion seen after chronic alcohol consumption contributes to the microcirculation disruption (21).…”

Section: Introductionmentioning

confidence: 83%

“…In a rat model of ALD, chronic alcohol consumption led to hepatic microcirculation disruption characterized by decreased red blood cell velocity and sinusoidal shutdown (21). This study suggested that increased leukocyte adhesion seen after chronic alcohol consumption contributes to the microcirculation disruption (21). However, the relationship between leukocyte infiltration and microcirculation disruption is still controversial.…”

Section: Introductionmentioning

confidence: 91%

“…The microcirculation disruption seen under both stress conditions is characterized by a hypersensitivity to the constrictor effects of endothelin-1 (ET-1), a potent vasoconstrictor expressed by LPS exposure as well as chronic alcohol consumption (26,27). Intravital microscopic assessment of the liver microcirculation of alcohol fed rats treated with LPS or saline suggested that chronic alcohol consumption can sensitize the liver microcirculation to the effects of LPS, leading to synergistic exacerbation of the disruption (21,27). A study conducted by Horie et al (27) suggested that alcohol-mediated blood flow disruption and sensitization to LPS were dependent on the effects of ET-1.…”

Section: Introductionmentioning

confidence: 98%

“…Stress-mediated inhibition of eNOS activity has been reported under mild stresses such as remote trauma and advanced liver diseases such as cirrhosis, and has been linked to upregulation of an eNOS inhibitor: caveolin-1 (CAV-1) (22,30). Although alcohol-mediated disruption of the liver microcirculation has been well characterized, the molecular mechanisms leading to this disruption have not yet been investigated (21,27).…”

Section: Introductionmentioning

confidence: 98%

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Chronic Ethanol Sensitizes the Liver to Endotoxin via Effects on Endothelial Nitric Oxide Synthase Regulation

Karaa

Kamoun²,

Clemens³

2005

Shock

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In vivo studies have shown that chronic alcohol consumption sensitizes the liver to endotoxemic shock, leading to liver microcirculation disruption. In the present study, we investigated the molecular mechanisms involved, focusing on endothelial nitric oxide synthase (eNOS) activity and regulation, which represents one of the major vasodilatory pathways. Male Sprague-Dawley rats were fed an alcohol liquid diet or a control isocaloric diet for 5 weeks. Priming effects of ethanol were studied in a model with or without a 24-h LPS treatment (1 mg/kg body weight). At the end of the diet, liver tissue was harvested for western blot, reverse transcriptase-PCR, histological analysis, and immunostaining and blood for serum alanine aminotransferase analysis. Chronic ethanol and LPS alone induced a mild hepatitis and infiltration, respectively. Combined, LPS and chronic ethanol feeding showed a synergistic effect on the liver, leading to extensive steatohepatitis with extensive focal necrosis associated with significantly higher levels of serum ALT. Chronic ethanol and LPS significantly inhibited eNOS activity, but exerted their effects through different mechanisms. Caveolin-1, an eNOS inhibitory protein, was upregulated after LPS and chronic alcohol consumption. Additionally, chronic alcohol consumption down-regulated endothelin B receptor, eNOS protein levels, and eNOS phosphorylation. In conclusion, chronic ethanol consumption and LPS share a similar pathophysiology and both lead to the impairment of eNOS activity, but through distinct molecular mechanisms. The presence of focal necrosis in a mild stress model could provide a good animal study to investigate the advanced stages of alcoholic liver diseases.

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Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Chronic Ethanol Sensitizes the Liver to Endotoxin via Effects on Endothelial Nitric Oxide Synthase Regulation

Karaa

Kamoun²,

Clemens³

2005

Shock

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“…Anti-CD18 monoclonal antibody (mAb) administration can attenuate hepatic injury, indicating a role for adhesion molecules in its pathogenesis [6]. Imaging of hepatic sinusoids and mesenteric venules in the rat model of chronic EtOH consumption has revealed that CD11a/CD18 (lymphocyte function-associated Ag [LFA]-1), CD18, and CD54 play significant roles in EtOH-induced increases in leukocyte adherence and extravasation [7,9,10], whereas higher serum levels of intercellular adhesion molecule are found in chronic alcohol users compared with nondrinkers or moderate drinkers [2].…”

Section: Introductionmentioning

confidence: 99%

Chronic ethanol exposure affects in vivo migration of hepatic dendritic cells to secondary lymphoid tissue

2007

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Parenchymal cell apoptosis as a signal for sinusoidal sequestration and transendothelial migration of neutrophils in murine models of endotoxin and fas-antibody-induced liver injury

et al. 1998

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Chronic Ethanol Consumption Enhances Endotoxin Induced Hepatic Sinusoidal Leukocyte Adhesion

Cited by 11 publications

References 12 publications

Chronic Ethanol Sensitizes the Liver to Endotoxin via Effects on Endothelial Nitric Oxide Synthase Regulation

Chronic Ethanol Sensitizes the Liver to Endotoxin via Effects on Endothelial Nitric Oxide Synthase Regulation

Chronic ethanol exposure affects in vivo migration of hepatic dendritic cells to secondary lymphoid tissue

Parenchymal cell apoptosis as a signal for sinusoidal sequestration and transendothelial migration of neutrophils in murine models of endotoxin and fas-antibody-induced liver injury

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