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. /sup 125/I-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.
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 5513899
- Journal Information:
- Gastroenterology; (United States), Journal Name: Gastroenterology; (United States) Vol. 94:2; ISSN GASTA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ALBUMINS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOLOGICAL PATHWAYS
BODY
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
ENZYME ACTIVITY
ENZYMES
EXTRACELLULAR SPACE
FUNCTIONS
HYDROLASES
INFECTIOUS DISEASES
INFECTIOUS HEPATITIS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPES
LIVER CELLS
MAMMALS
MAN
MEMBRANE PROTEINS
METABOLISM
MICROORGANISMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PARASITES
PERFUSED ORGANS
POLYMERS
PRIMATES
PROTEINS
RADIOISOTOPES
RATS
RECEPTORS
RODENTS
SOMATIC CELLS
SPACE
TISSUES
UPTAKE
VERTEBRATES
VIRAL DISEASES
VIRUSES