Scavenger Receptors on Sinusoidal Liver Endothelial Cells Are Involved in the Uptake of Aldehyde-Modified Proteins

  1. Michael J. Duryee,
  2. Thomas L. Freeman,
  3. Monte S. Willis1,
  4. Carlos D. Hunter,
  5. Bartlett C. Hamilton III,
  6. Hiroshi Suzuki2,
  7. Dean J. Tuma,
  8. Lynell W. Klassen and
  9. Geoffrey M. Thiele
  1. Departments of Internal Medicine (M.J.D., T.L.F., C.D.H., B.C.H., D.J.T., L.W.K., G.M.T.) and Pathology and Microbiology (G.M.T.), University of Nebraska Medical Center, Omaha, Nebraska; and Veterans Administration Alcohol Research Center, Omaha Veterans Administration Medical Center, Omaha, Nebraska (M.J.D., T.L.F., M.S., C.D.H., B.C.H., H.S., D.J.T., L.W.K., G.M.T.)
  1. Address correspondence to:
    Michael J. Duryee, Omaha VA Medical Center, Research Services 151, Room 325, 4101 Woolworth Avenue, Omaha, NE 68105. E-mail: mduryee{at}unmc.edu

Abstract

Scavenger receptors on sinusoidal liver endothelial cells (SECs) eliminate potentially harmful modified proteins circulating through the liver. It was shown recently that aldehyde-modified proteins bind to scavenger receptors and are associated with the development/progression of alcoholic liver diseases. For these studies, rat livers were perfused in situ with 125I-formaldehyde-bovine serum albumin (f-Alb) or 125I-malondialdehyde-acetaldehyde-bovine serum albumin (MAA-Alb) in the presence of known scavenger receptor ligands as inhibitors. Reverse transcription-polymerase chain reaction (RT-PCR) analysis and scavenger receptor Type A (SRA) knock-out mice were used to assess the role of these receptors in mediating immune responses. The degradation of 125I-f-Alb or 125I-MAA-Alb in whole livers and isolated SECs can be inhibited by known scavenger receptor ligands, including f-Alb, maleylated bovine albumin, and fucoidan. 125I-f-Alb could not be completely inhibited by MAA-Alb. In contrast, 125I-MAA-Alb was only partially inhibited with advanced glycosylated endproduct albumin. RT-PCR data show the presence of a number of scavenger receptors on SECs that may be responsible for the binding of MAA-modified proteins. SRA seems to be one of these receptors involved in the effects mediated by MAA-modified proteins. In a study using SRA knockout mice, it was shown that a decreased antibody response to MAA-Alb resulted. By RT-PCR, CD36, LOX-1, and SR-AI are the scavenger receptors most likely involved in the degradation of MAA-Alb.

Footnotes

  • This work was supported by National Institutes of Health grants R29-AA10435, R01-AA07818, and R01-AA04961 and by the Department of Veterans Affairs Alcohol Research Center.

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

  • doi:10.1124/mol.105.016121.

  • ABBREVIATIONS: f-Alb, formaldehyde-modified albumin; Alb, bovine serum albumin; AGE, advanced glycation end-products; Maley-Alb, maleylated bovine albumin; SEC, sinusoidal liver endothelial cell; MAA, malondialdehyde-acetaldehyde adduct; RT, reverse transcription; PCR, polymerase chain reaction; bp, base pair(s); SRA, scavenger receptor A; KO, knockout; WT, wild type; TNF, tumor necrosis factor.

  • ↵1 Current affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC.

  • ↵2 Current affiliation: National Research Center for Protozoan Disease, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.

    • Received June 28, 2005.
    • Accepted August 15, 2005.
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  1. Published online before print August 16, 2005, doi: 10.1124/mol.105.016121 Molecular Pharmacology November 2005 vol. 68 no. 5 1423-1430
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