Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol-injured liver
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The consumption of alcohol is associated with many health issues including alcoholic liver disease (ALD). The natural history of ALD involves the development of steatosis, inflammation (steatohepatitis), fibrosis and cirrhosis. During the stage of steatohepatitis, the combination of inflammation and cellular damage can progress to a severe condition termed alcoholic hepatitis (AH). Unfortunately, the pathogenesis of AH remains uncharacterized. Some modulations have been identified in host defense and liver immunity mechanisms during AH that highlight the role of intrahepatic lymphocyte accumulation and associated inflammatory cytokine responses. Also, it is hypothesized that alcohol-induced injury to liver cells may significantly contribute to the aberrant lymphocytic distribution that is seen in AH. In particular, the regulation of lymphocytes by hepatocytes may be disrupted in the alcoholic liver resulting in altered immunologic homeostasis and perpetuation of disease. In recent studies, it was demonstrated that the direct killing of activated T lymphocytes by hepatocytes is facilitated by the asialoglycoprotein receptor (ASGPR). The ASGPR is a well-characterized glycoprotein receptor that is exclusively expressed by hepatocytes. This hepatic receptor is known for its role in the clearance of desialylated glycoproteins or cells, yet neither its physiological function nor its role in disease states has been determined. Interestingly, alcohol markedly impairs ASGPR function; however, the effect alcohol has on ASGPR-mediated cytotoxicity of lymphocytes remains to be elucidated. This review discusses the contribution of hepatocytes in immunological regulation and, importantly, how pathological effects of ethanol disrupt hepatocellular-mediated defense mechanisms.
KeywordsAlcoholic liver disease Alcoholic hepatitis Asialoglycoprotein receptor Intrahepatic lymphocytes Receptor-mediated endocytosis
Compliance with ethical requirements and Conflict of interest
This article does not contain any studies with human or animal subjects performed by any of the authors. Benita L. McVicker, Geoffrey M. Thiele, Dean J. Tuma, and Carol A. Casey declare that they have no conflict of interest.
- 1.World Health Organization. Global Status Report on Alcohol and Health 2011. Geneva: WHO Library; 2011. 20–37Google Scholar
- 2.Mailliard ME, Sorrell MF. Alcoholic liver disease. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine. New York: The McGraw-Hill Companies, Inc; 2008. 1969–1973Google Scholar