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Survival of recombinant erythropoietin in the circulation: the role of
carbohydrates
MN Fukuda, H Sasaki, L Lopez and M Fukuda
La Jolla Cancer Research Foundation, Cancer Research Center, CA 92037.
Recombinant human erythropoietin produced in transfected Chinese hamster
ovary cells is glycosylated much the same way as the erythropoietin present
in human urine. To determine the role of carbohydrates in the stability of
recombinant human erythropoietin in vivo, [125I]-labeled recombinant
erythropoietin was intravenously infused into rats. The erythropoietin was
slowly cleared from the blood with a half-life of approximately two hours.
Asialoerythropoietin, which was produced by treatment of recombinant human
erythropoietin with sialidase, was found to be cleared rapidly from
circulation within ten minutes. These data suggest that the galactose
binding protein of hepatic cells is involved in the clearance of
asialoerythropoietin. Erythropoietin also contains N-glycans with a few
N-acetyllactosamine repeats, which can be enriched by tomato lectin
affinity chromatography. The lectin-bound fraction was cleared to a larger
extent than was the unfractionated erythropoietin, while the component that
did not bind the lectin was found to be stable in the circulation.
Authentic N-acetyllactosamine repeats (polylactosaminoglycans) prepared
from erythrocytes were similarly rapidly cleared from the circulation to
the liver, and this clearance was inhibitable with asialo-alpha 1- acid
glycoprotein. These results suggest that (a) the sialic acid of the
recombinant erythropoietin is necessary for this glycoprotein hormone to
circulate stably and (b) glycoproteins with more than three lactosaminyl
repeat units may be cleared by the galactose binding protein of
hepatocytes.
Volume 73,
Issue 1,
pp. 84-89,
01/01/1989
Copyright © 1989 by The American Society of Hematology
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