Leukocyte low density lipoprotein receptor (LDL-R) does not contribute to LDL clearance in vivo: Bone marrow transplantation studies in the mouse

Sergio Fazio, Alyssa H. Hasty, Kathy J. Carter, Alisa B. Murray, James O. Price, MacRae R F Linton

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The targeted disruption of the low density lipoprotein (LDL) receptor gene in mice results in accumulation of plasma LDL cholesterol and in predisposition to diet-induced aortic atherosclerosis. Although the liver is the central organ for receptor mediated clearance of LDL, the in vivo role of other organs and tissues in LDL catabolism has not been directly studied. Since bone marrow-derived cells such as blood leukocytes and tissue macrophages express LDL receptors and contribute a large cell mass to the body, we designed bone marrow transplantation (BMT) experiments to reconstitute LDL receptor null mice [LDL-R(-/-)] with marrow obtained from LDL-R wild-type mice [(+/+)] and evaluate the effects of parameters of plasma lipid metabolism. Although reconstitution of the transplanted mice with donor bone marrow cells was complete, no differences in plasma lipid levels and lipoprotein distribution were found between groups, irrespective of the diet used, and turnover studies using 125I-labeled LDL showed that LDL receptor expression by leukocytes and macrophages does not significantly contribute plasma LDL clearance. The complementary experiment of transplanting LDL-R(-/-) marrow into C57BL/6 recipients [LDL-R(-/- )→LDL(+/+)], performed to evaluate the role of leukocyte LDL-R in normocholesterolemic conditions, also produced no effects on plasma lipid parameters. LDL binding studies using macrophages isolated from transplanted mice showed a lack of LDL-R expression. Thus, despite their large number and wide distribution, bone marrow-derived cells do not significantly influence receptor-mediated clearance of plasma LDL.

Original languageEnglish (US)
Pages (from-to)391-400
Number of pages10
JournalJournal of Lipid Research
Volume38
Issue number2
StatePublished - Feb 1997
Externally publishedYes

Fingerprint

LDL Receptors
Bone Marrow Transplantation
LDL Lipoproteins
Bone
Leukocytes
Plasmas
Macrophages
Bone Marrow Cells
Nutrition
Bone Marrow
Tissue
Diet
Lipids
Lipid Metabolism
Liver
LDL Cholesterol
Lipoproteins
Atherosclerosis
Blood
Genes

Keywords

  • bone marrow transplantation
  • dyslipidemias
  • familial hypercholesterolemia
  • gene delivery
  • macrophages
  • mouse models

ASJC Scopus subject areas

  • Endocrinology

Cite this

Leukocyte low density lipoprotein receptor (LDL-R) does not contribute to LDL clearance in vivo : Bone marrow transplantation studies in the mouse. / Fazio, Sergio; Hasty, Alyssa H.; Carter, Kathy J.; Murray, Alisa B.; Price, James O.; Linton, MacRae R F.

In: Journal of Lipid Research, Vol. 38, No. 2, 02.1997, p. 391-400.

Research output: Contribution to journalArticle

Fazio, Sergio ; Hasty, Alyssa H. ; Carter, Kathy J. ; Murray, Alisa B. ; Price, James O. ; Linton, MacRae R F. / Leukocyte low density lipoprotein receptor (LDL-R) does not contribute to LDL clearance in vivo : Bone marrow transplantation studies in the mouse. In: Journal of Lipid Research. 1997 ; Vol. 38, No. 2. pp. 391-400.
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