Biochemical and genetic studies of the apoprotein E secreted by mouse macrophages and human monocytes

S. K. Basu, Y. K. Ho, M. S. Brown, D. W. Bilheimer, R. G. Anderson, J. L. Goldstein

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199 Scopus citations

Abstract

Monolayers of mouse peritoneal macrophages secrete large amounts of apoliprotein E (apo-E) after the cells have been loaded with cholesterol by incubation with modified lipoproteins. In the current studies, we characterize some of the biochemical morphological, and functional properties of macrophage-secreted apo-E, and we also show that a similar protein is secreted by human blood monocytes. Apo-E was secreted by mouse macrophages in the form of lipoprotein particles with a mean density of 1.075 g/ml. By electron microscopy, these lipoproteins appeared as lamellar discs. The 35S-labeled apo-E secreted by macrophages was able to bind to low density lipoprotein receptors on human fibroblasts and was taken up and degraded with high affinity. The 35S-labeled apo-E secreted by human monocytes was examined by two-dimensional isoelectric focusing-sodium dodecyl sulfate polyacrylamide gel electrophoresis. The secreted protein was more acidic than the apo-E of plasma very low density lipoprotein from the same individual. Treatment with neuramidase converted the monocyte-produced apo-E to a form that resembled plasma apo-E, suggesting that the secreted product had more sialic acid residues than the circulating form. Monocytes from individuals with different alleles at the genetic locus specifying apo-E secreted a form of 35S-labeled apo-E that was electrophoretically similar to their plasma apo-E after neuraminidase treatment, suggesting that the monocyte-secreted apo-E and the plasma apo-E are products of the same gene. The finding that cholesterol-loaded macrophages and monocytes synthesize and secrete apo-E is discussed in relation to the in vivo process of 'reverse cholesterol transport.'

Original languageEnglish (US)
Pages (from-to)9788-9795
Number of pages8
JournalJournal of Biological Chemistry
Volume257
Issue number16
StatePublished - Dec 1 1982

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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