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• W2050874860 endingPage "1651" @default.
• W2050874860 startingPage "1643" @default.
• W2050874860 abstract "Macrophages internalize aggregated low density lipoprotein (LDL) by LDL receptor-dependent phagocytosis. To investigate this model of foam cell formation, we have used human and mouse macrophages to characterize biochemically and morphologically the fate of ingested phospholipase C-modified low density lipoprotein (PLC-LDL). When LDL was digested with phospholipase C, it lost phospholipid and aggregated. Human monocyte-derived macrophages rapidly ingested and degraded 125I-PLC-LDL. The degraded PLC-LDL released free cholesterol, measured either as free sterol mass or by the stimulation of [14C]oleate incorporation into cellular cholesteryl ester. Esterification was blocked by chloroquine, a weak base that inhibits lysosomal degradation. Macrophages exposed to PLC-LDL exhibited a 30-fold to a 50-fold increase in esterified sterol: by light microscopy, cytoplasmic inclusions were abundant. The inclusions were stained with oil red O, indicating that they were neutral lipid droplets. By electron microscopy, mouse peritoneal macrophages incubated with PLC-LDL contained numerous membrane-bounded vacuoles and cytoplasmic inclusions that were not surrounded by a limiting membrane. Pulse-chase experiments demonstrated that vacuoles filled with particulate material appeared first. Subsequently, the macrophages exhibited vacuoles containing multivesicular bodies. Last, inclusions that were homogeneously electron-dense and that lacked a tripartite membrane accumulated in the cytoplasm of the cells. These results are consonant with the following model of foam cell formation. Cultured macrophages rapidly ingest PLC-LDL that is initially localized in phagosomes. The aggregated lipoprotein subsequently is digested in secondary lysosomes, thus releasing free cholesterol that is reesterified, forming cytoplasmic cholesteryl ester droplets lacking a tripartite membrane." @default.
• W2050874860 created "2016-06-24" @default.
• W2050874860 creator A5022745436 @default.
• W2050874860 creator A5035595391 @default.
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• W2050874860 date "1991-11-01" @default.
• W2050874860 modified "2023-10-18" @default.
• W2050874860 title "Phagocytosis of lipase-aggregated low density lipoprotein promotes macrophage foam cell formation. Sequential morphological and biochemical events." @default.
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• W2050874860 doi "https://doi.org/10.1161/01.atv.11.6.1643" @default.
• W2050874860 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/1657129" @default.
• W2050874860 hasPublicationYear "1991" @default.
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