Review articleNeutrophil-mediated tissue injury in alcoholic hepatitis☆
Introduction
Alcoholic hepatitis is a serious complication of chronic alcohol abuse in human beings. Pathological evaluations of liver tissues have demonstrated the presence of polymorphonuclear leukocytes (neutrophils) in the parenchyma Hall 1985, Takahashi et al. 1987. Most investigators agree that neutrophils may contribute greatly to the pathological findings. However, direct proof for the involvement of neutrophils in the tissue injury during alcoholic hepatitis and insight into the mechanism of cell damage are currently not available. Nevertheless, during the past decade, substantial progress has been made in the general understanding of neutrophil-induced injury mechanisms in the liver Jaeschke 1997, Jaeschke & Smith 1997. The aim of this review is to summarize the current knowledge on neutrophil cytotoxicity and relate this information to pathological findings of alcoholic hepatitis.
Section snippets
Mechanisms of neutrophil-induced liver injury
In a number of experimental models, there is clear evidence that neutrophils contribute greatly to liver dysfunction and cell injury. These models include hepatic ischemia-reper- fusion (Jaeschke et al., 1990), endotoxemia (Jaeschke et al., 1991b), sepsis (Molnar et al., 1997), hemorrhagic shock and resuscitation (Bauer et al., 1995), remote organ trauma (Hill et al., 1992), and certain drug toxicities (Dahm et al., 1991). For neutrophils to cause injury to hepatocytes, they have to go through
Pathological features of alcoholic hepatitis in human beings
Examination of liver biopsy specimens obtained from patients with acute alcoholic hepatitis has revealed prominent neutrophil infiltration Hall 1985, Takahashi et al. 1987. These neutrophils are generally extravasated and located close to hepatocytes, which demonstrate various degrees of degeneration and cell necrosis. Furthermore, many neutrophils have their primary and secondary granules released (Takahashi et al., 1987). These findings are consistent with a neutrophil attack on hepatocytes
Future directions
On the basis of this discussion, a high priority in future research has to be to develop a relevant animal model of alcoholic hepatitis. The experience with different animal models of neutrophil-induced liver injury shows that activation and recruitment of neutrophils into the liver vasculature and their transmigration and attack on parenchymal cells are highly complex processes, which require an initiating event. At present, only a limited number of scenarios are known to trigger such a severe
Acknowledgements
Studies from my laboratory were supported in part by National Institutes of Health grants GM-42957, ES-06091, and AA-12916.
References (48)
- et al.
Distinct patterns of chemokine expression are associated with leukocyte recruitment of alcoholic hepatitis and alcoholic cirrhosis
J Pathol
(1998) - et al.
A natural glycoprotein inhibitor (NIF) of CD11b/CD18 reduces leukocyte adhesion in the liver after hemorrhagic shock
Shock
(1995) Chronic alcohol intoxication induces hepatic injury through enhanced macrophage inflammatory protein-2 production and intercellular adhesion molecule-1 expression in the liver
Hepatology
(1997)Neutrophilic infiltration in alcoholic hepatitis
Alcohol
(2002)- et al.
Endotoxin induced hepatic necrosis in rats on an alcohol diet
J Pathol
(1987) - et al.
Listeria monocytogenes infection increases neutrophil adhesion and damage to a murine hepatocyte cell line in vitro
Immunol Lett
(1995) - et al.
Neutrophil margination and extravasation in sinusoids and venules of liver during endotoxin-induced injury
Am J Physiol
(1997) - et al.
The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat
Hepatology
(1996) - et al.
Chemotactic activity of the lipid peroxidation product 4-hydroxynonenal and homologous hydroxyalkenals
Biol Chem Hoppe Seyler
(1986) - et al.
An antibody to neutrophils attenuates alpha-naphthylisothiocyanate-induced liver injury
J Pharmacol Exp Ther
(1991)
Transcriptional activation of vascular cell adhesion molecule-1 gene in vivo and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock
J Immunol
Cytokine-induced upregulation of hepatic intercellular adhesion molecule-1 messenger RNA expression and its role in the pathophysiology of murine endotoxin shock and acute liver failure
Hepatology
Inhibition of NF-κB activation by dimethyl sulfoxide correlates with suppression of TNF-α formation, reduced ICAM-1 gene transcription and protection against endotoxin-induced liver injury
Shock
Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock
J Leukoc Biol
Differential induction of mRNA for ICAM-1 and selectins in hepatocytes, Kupffer cells and endothelial cells during endotoxemia
Biochem Biophys Res Commun
Endotoxin-induced activation of the nuclear transcription factor κB and expression of E-selectin messenger RNA in hepatocytes, Kupffer cells, and endothelial cells in vivo
J Immunol
Intercellular adhesion molecule-1 (ICAM-1) expression and its role in neutrophil-induced ischemia-reperfusion injury in the liver
J Leukoc Biol
Pathology and pathogenesis of alcoholic liver disease
A Mac-1 antibody reduces liver and lung injury but not neutrophil sequestration after intestinal ischemia-reperfusion
Surgery
Reactive oxygen and ischemia/reperfusion injury of the liver
Chem Biol Interact
Cellular adhesion moleculesregulation and functional significance in the pathogenesis of liver diseases
Am J Physiol
Reactive oxygen and mechanisms of inflammatory liver injury
J Gastroenterol Hepatol
Superoxide generation by Kupffer cells and priming of neutrophils during reperfusion after hepatic ischemia
Free Radic Res Commun
Superoxide generation by neutrophils and Kupffer cells during in vivo reperfusion after hepatic ischemia in rats
J Leukoc Biol
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