Sphingomyelinase enhances low density lipoprotein uptake and ability to induce cholesteryl ester accumulation in macrophages

Xiangxi Xu, Ira Tabas

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Cholesteryl ester-loaded macrophages, or foam cells, are a prominent feature of atherosclerotic lesions. Low density lipoprotein (LDL) receptor-mediated endocytosis of native LDL is a relatively poor inducer of macrophage cholesteryl ester accumulation. However, the data herein show that in the presence of a very small amount of aphingomyelinase, LDL receptor-mediated endocytosis of 125I-LDL was enhanced and led to a 2-6-fold increase in 125I-LDL degradation and up to a 10-fold increase in cholesteryl ester accumulation in macrophages. The enhanced lipoprotein uptake and cholesterol esterification was seen after only ∼12% hydrolysis of LDL phospholipids, was specific for sphingomyelin hydrolysis, and appeared to be related to the formation of fused or aggregated spherical particles up to 100 nm in diameter. Sphingomyelinase-treated LDL was bound by the macrophage LDL receptor. However, when unlabeled acetyl-LDL, a scavenger receptor ligand, was present during or after sphingomyelinase treatment of 125I-LDL, 125I-LDL binding and degradation were enhanced further through the formation of LDL-acetyl-LDL mixed aggregates. Experiments with cytochalasin D suggested that endocytosis, not phagocytosis, was involved in internalization of sphingomyelinase-treated LDL. Nonetheless, the sphingomyelinase effect on LDL uptake was macrophage-specific. These data illustrate that LDL receptor-mediated endocytosis of fused LDL particles can lead to foam cell formation in cultured macrophages. Furthermore, since both LDL and sphingomyelinase are present in atherosclerotic lesions and since some lesion LDL probably is fused or aggregated, there is a possibility that sphingomyelinase-treated LDL is a physiologically important atherogenic lipoprotein.

Original languageEnglish
Pages (from-to)24849-24858
Number of pages10
JournalJournal of Biological Chemistry
Volume266
Issue number36
StatePublished - Dec 25 1991
Externally publishedYes

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Sphingomyelin Phosphodiesterase
Cholesterol Esters
Macrophages
LDL Lipoproteins
LDL Receptors
Endocytosis
Foam Cells
Lipoproteins
Foams
Hydrolysis
Cytochalasin D
Scavenger Receptors
Degradation
Sphingomyelins
Esterification
Phagocytosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sphingomyelinase enhances low density lipoprotein uptake and ability to induce cholesteryl ester accumulation in macrophages. / Xu, Xiangxi; Tabas, Ira.

In: Journal of Biological Chemistry, Vol. 266, No. 36, 25.12.1991, p. 24849-24858.

Research output: Contribution to journalArticle

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