Modification of Proteins by Reactive Ethanol Metabolites: Adduct Structure, Functional and Pathological Consequences

Simon Worrall, Geoffrey M. Thiele

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations

Abstract

This chapter focuses on the modification of proteins by reactive ethanol metabolites and the pathological consequences. Although the exact pathophysiology of Alcoholic Liver Disease (ALD) remains unsolved, there is substantial evidence that altered immune reactivity occurs as a consequence of alcohol ingestion in both humans and animal models. Clinically, the association of circulating autoantibodies, hypergammaglobulinemia, antibodies to unique hepatic proteins, and cytotoxic lymphocytes reacting against autologous hepatocytes, strongly suggests altered immune regulation with a relative loss of self-tolerance. The significant immune responses generated that specifically recognized self-proteins that are modified by metabolites of alcohol, also suggest the significant role that immune reactions may play in inducing and/or sustaining an inflammatory cascade of tissue damage in the liver. While ethanol and its metabolites are too small to act as immunogens, acting as haptens, they could produce changes in the membranes of hepatocytes. Evidence in the favor of this is provided by the demonstration of antibodies reactive with ethanol-altered hepatocytes, and the presence of circulating cytotoxic lymphocytes reactive with autologous hepatocytes. The histological appearances of the various forms of ALD are also suggestive of a chronic active hepatitis-like inflammatory disease.

Original languageEnglish (US)
Title of host publicationComprehensive Handbook of Alcohol Related Pathology
PublisherElsevier Inc.
Pages1209-1222
Number of pages14
Volume3-3
ISBN (Electronic)9780080502311
ISBN (Print)9780125643702
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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