Scavenger receptors on sinusoidal liver endothelial cells are involved in the uptake of aldehyde-modified proteins.
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.
Duryee
Michael J
MJ
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, Omaha, NE 68105, USA. mduryee@unmc.edu
Freeman
Thomas L
TL
Willis
Monte S
MS
Hunter
Carlos D
CD
Hamilton
Bartlett C
BC
Suzuki
Hiroshi
H
Tuma
Dean J
DJ
Klassen
Lynell W
LW
Thiele
Geoffrey M
GM
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000378:metabolism
D000447:Aldehydes; D011506:Proteins; D012710:Serum Albumin, Bovine; D000431:Ethanol