Collagen-acetaldehyde adducts in alcoholic and nonalcoholic liver diseases

Authors

  • Gianluca Svegliati-Baroni,

    1. Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, and the Mount Sinai School of Medicine, New York, New York 10468
    Current affiliation:
    1. Department of Gastroenterology, University of Ancona, Ancona, Italy
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  • Enrique Baraona,

    1. Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, and the Mount Sinai School of Medicine, New York, New York 10468
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  • Alan S. Rosman,

    1. Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, and the Mount Sinai School of Medicine, New York, New York 10468
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  • Charles S. Lieber MD

    Corresponding author
    1. Alcohol Research and Treatment Center, Bronx Veterans Affairs Medical Center, and the Mount Sinai School of Medicine, New York, New York 10468
    • Alcohol Research and Treatment Center, Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468
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Abstract

Alcoholic and, to a lesser extent, nonalcoholic patients with liver disease have serum antibodies to acetaldehyde-protein adducts produced in vitro. These antibodies presumably reflect the presence of adducts in the liver, but the protein that triggers this immune response has not been identified. To study this, we measured the reactivity of cytosolic proteins to rabbit IgG developed against a P-450 2E1—acetaldehyde adduct, isolated from alcohol-fed rats, that recognizes acetaldehyde-modified epitopes in proteins. Adducts were determined on Western blots by scanning densitometry of antibody-linked alkaline phosphatase activity in 4 normal livers and in needle biopsy specimens from subjects with liver disease, 17 alcoholic and 14 nonalcoholic. In all livers, except for a normal one, we found a reactive protein of at least 200 kD, similar to the collagen-acetaldehyde adduct we reported to be markedly increased in rats with experimentally induced cirrhosis. The immunostaining intensity in the alcoholic patients with liver disease was eightfold (p<0.01) and that in nonalcoholic patients with liver disease was fourfold, greater (p<0.02) than the weak staining in normal livers; it correlated with the degree of inflammation and serum AST or γ-glutamyl transpeptidase activities. The adduct was reproduced on incubation of normal cytosolic proteins with 2.5 mmol/L acetaldehyde, whereas higher concentrations yielded many additional adducts; the adduct also reacted with IgG antibody to rat collagen type I and disappeared after digestion with collagenase, suggesting that the target protein is a form of collagen. The association of this collagen-acetaldehyde adduct with parameters of liver disease activity suggests that the adduct reflects the liver injury and may even contribute to its development, both in alcoholic and in nonalcoholic subjects. (Hepatology 1994;20:111–118.)

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