Failure of the intracellular itinerary of β very low density lipoproteins to augment cholesterol esterification in macrophages from watanabe heritable hyperlipidemic rabbits

A. Daugherty, D. L. Rateri

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

β very low density lipoproteins (β-VLDL) interact with mouse peritoneal macrophages via specific receptors leading to pronounced stimulation of cholesterol esterification. The present study has defined an alternative pathway for the processing of β-VLDL in alveolar macrophages from Watanabe heritable hyperlipidemic (WHHL) rabbits. Macrophages from either New Zealand (NZ) or WHHL rabbits degraded 125I-β-VLDL to an equivalent extent. Degradation was competed to a similar extent in both cell types by either excess unlabeled β-VLDL or low density lipoprotein, indicative of a specific receptor involvement. Accumulation of intracellular degradation products of β-VLDL labeled with the residualizing label, dilactitol-125I-tyramine, was similar in both cell types demonstrating that degradation was not due to secreted proteolytic enzymes. β-VLDL promoted the incorporation of [3H] oleate into cholesteryl-[3H]oleate and increased the cellular mass of cholesterol in NZ macrophages. In contrast, β-VLDL did not augment cholesteryl-[3H]oleate deposition in WHHL macrophages. This lack of cholesterol esterification occurred despite equivalent acylCoA:cholesterol acyltransferase activity in microsomal fractions of both cell types, and similar augmentations in cholesteryl-[3H]oleate during incubation with phospholipase C-treated LDL. Incubation of WHHL macrophages with β-VLDL increased cellular cholesterol mass, although the response was attenuated compared to NZ cells. To determine whether these disparities in cholesterol esterification were related to the catabolic fate of β-VLDL-derived cholesterol esters, [3H]cholesteryl oleate was exchanged into the core of β-VLDL and incubated with macrophages in medium containing [14C]oleate. NZ macrophages accumulated both [3H] cholesterol and [3H]cholesteryl-[14C]oleate after 5 h, indicating hydrolysis and re-esterification of cholesterol esters. In contrast, WHHL macrophages only accumulated [3H]cholesterol esters, suggesting uptake of cholesterol esters without subsequent hydrolysis. These data demonstrate that WHHL macrophages possess a pathway for the intracellular processing of β-VLDL that permits internalization of the particle without stimulation of cholesterol esterification.

Original languageEnglish
Pages (from-to)17269-17275
Number of pages7
JournalJournal of Biological Chemistry
Volume266
Issue number26
StatePublished - Sep 15 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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