Uptake and metabolism of polymerized albumin by rat liver. Role of the scavenger receptor.
Hepatitis B virus binds avidly to albumin polymers, which in turn may mediate viral attachment to liver cells. This hypothesis is critically dependent on prior results obtained using glutaraldehyde-polymerized human serum albumin as a model for naturally occurring albumin species. We used the perfused rat liver to characterize the uptake, cellular distribution, and metabolism of glutaraldehyde-polymerized human albumin. 125I-glutaraldehyde-polymerized human albumin was efficiently removed from the perfusate by the liver (29% extraction). However, few autoradiographic grains were located over hepatic parenchymal cells (6%). Instead, most glutaraldehyde-polymerized human albumin appeared to be removed by endothelial (59%) or Kupffer (31%) cells. Hepatic uptake was strongly inhibited by formaldehyde-treated monomeric albumin, a known ligand of the endothelial scavenger receptor for chemically modified proteins. After uptake, most glutaraldehyde-polymerized human albumin was rapidly degraded and released into the perfusate (74% within 60 min). This process was blocked by chloroquine and leupeptin, suggesting that it involves lysosomal acid hydrolases. We conclude that glutaraldehyde-polymerized albumin is efficiently cleared and degraded by the endothelial scavenger pathway. Glutaraldehyde-polymerized albumin therefore appears to be a poor model for predicting the hepatic handling of naturally occurring albumin species bound to hepatitis B virions. Even if viral particles were to follow this pathway, few would enter parenchymal hepatocytes.
Wright
T L
TL
Department of Medicine, University of California, San Francisco.
Roll
F J
FJ
Jones
A L
AL
Weisiger
R A
RA
D000818:Animals; D001345:Autoradiography; D004727:Endothelium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005976:Glutaral; D007457:Iodine Radioisotopes; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D011108:Polymers; D051381:Rats; D011919:Rats, Inbred Strains; D017457:Receptors, Albumin; D011956:Receptors, Cell Surface / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012709:Serum Albumin / Q000378:metabolism*
D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D011108:Polymers; D017457:Receptors, Albumin; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D012709:Serum Albumin; D005976:Glutaral