Hepatic targeting and hypocholesterolemic effect of lactosaminated Fab against low density lipoproteins
Lactosaminated Fab (lac-Fab) specific for human LDL induces plasma clearance and uptake of circulating (/sup 125/-I)-iodo-LDL in rat, a process mediated by galactose receptors of the liver. This study demonstrates that lac-Fab is a specific carrier of LDL to the liver parenchymal cells and exhibits hypocholesterolemic activity in vivo. Rats were injected with fluorescent 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-LDL (diI-LDL) or 6 mg of LDL plus tracer amounts of (/sup 125/I)-iodo-LDL. After 10-20 min, the animals received 3-10 mg of lac-Fab. Histologic examination of the liver sections showed the uptake of diI-LDL in the parenchymal cells, as compared to diI-acetyl-LDL which was localized in sinusoidal cells. More than 85% of human LDL disappeared within 2.5 hr after lac-Fab injection, reducing plasma cholesterol from 133.0 +/- 12.6 mg/dl to 66.4 +/- 8.0 mg/dl, the basal value in the rat. In control rats, only about 20% of radioactivity and cholesterol disappeared at 2.5 hr. HDL levels were unaffected. The authors conclude that lac-Fab is a specific carrier of LDL to hepatocytes and can lower plasma LDL-cholesterol in vivo. Lac-Fab specific for other antigens may act as specific carriers of molecule or macromolecules to hepatocytes.
- Research Organization:
- Baylor College of Medicine, Houston, TX
- OSTI ID:
- 5332221
- Report Number(s):
- CONF-8604222-; TRN: 86-031457
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
IMMUNOGLOBULINS
BIOLOGICAL FUNCTIONS
LIPOPROTEINS
BLOOD-PLASMA CLEARANCE
UPTAKE
CHOLESTEROL
IODINE 125
LIVER CELLS
RATS
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
CLEARANCE
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
FUNCTIONS
GLOBULINS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIPIDS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
RODENTS
SOMATIC CELLS
STEROIDS
STEROLS
VERTEBRATES
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