Metabolism of normal and modified low-density lipoproteins by macrophage cell lines of murine and human origin

David P. Via, Anne L. Plant, Iain F. Craig, Antonio M. Gotto, Louis C. Smith

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Four murine macrophage-like continuous cell lines (P388D1, J774.1, RAW 264.7, and PU5-1.8) and two human cell lines displaying macrophage-monocyte characteristics (HL-60, U-937) have been examined for their ability to degrade both normal and acetylated low-density lipoproteins. All of these cell lines, except PU5-1.8, were demonstrated to have LDL receptors that were induced 2-5-fold by preincubation in lipoprotein-deficient serum. Metabolism of dextran sulfate-LDL complexes by all lines except PU5-1.8 was observed. Three cell lines, P388D1, J774.1 and RAW 264.7, while exhibiting individual differences in their metabolism of acetyl-LDL, all processed acetyl-LDL in a fashion qualitatively analogous to that by murine peritoneal macrophages and human monocytes. Cell lines PU5-1.8, U-937 and HL-60 did not bind or degrade significant quantities of acetyl-LDL. In P388D, cells, metabolism of acetyl-LDL exhibited time and concentration dependence, was reversibly inhibited by chloroquine, blocked by fucoidan and dextran sulfate, and was calcium independent. Approximately 4 · 105 receptors, with an apparent Kd of 3 · 10-8 M, were present on P388D1 cells. P388D1 cells metabolized 30% as much acetyl-LDL as murine peritoneal macrophages at 37°C and bound 60% as much at 4°C. Chemical measurement demonstrated a 250-fold increase in the cholesteryl ester content of P388D1 cells over 96 h. The accumulation of cholesteryl esters was reversible in the presence of HDL3 and involved continuous hydrolysis and reesterification. These lines represent a convenient resource for examining the metabolism of chemically modified lipoproteins, for isolation of cell mutants, and for isolation of specific lipoprotein receptors.

Original languageEnglish (US)
Pages (from-to)417-428
Number of pages12
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume833
Issue number3
DOIs
StatePublished - Mar 6 1985

Keywords

  • (Human, murine macrophage-monocyte cell line)
  • Acetyl-LDL
  • Cholesterol
  • Foam cell
  • Lipoprotein receptor

ASJC Scopus subject areas

  • Endocrinology
  • Biophysics
  • Biochemistry

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