Scavenger receptors on sinusoidal liver endothelial cells are involved in the uptake of aldehyde-modified proteins

Michael J. Duryee, Thomas L. Freeman, Monte S. Willis, Carlos D. Hunter, Bartlett C. Hamilton, Hiroshi Suzuki, Dean J. Tuma, Lynell Warren Klassen, Geoffrey Milton Thiele

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1423-1430
Number of pages8
JournalMolecular pharmacology
Volume68
Issue number5
DOIs
StatePublished - Nov 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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