Apolipoprotein E expression by human-monocyte-derived macrophages. Modulation by opsonised zymosan and cholesterol.
The effects of opsonised zymosan and of acetylated low-density lipoprotein (AcLDL) on the synthesis and secretion of apolipoprotein E (apoE), and of apoE mRNA abundance, have been studied in human-monocyte-derived macrophages (MDM). Stimulation by opsonised zymosan led to a concentration-dependent increase in apoE secretion; non-opsonised zymosan was without effect. Incubation with AcLDL led to a concentration-dependent elevation in apoE synthesis which paralleled the increase in cellular cholesterol content. The opsonised-zymosan-induced stimulation of apoE production was additive to that resulting from cholesterol loading with AcLDL. Opsonised zymosan alone did not affect the cholesterol content of MDM. Cholesterol-loaded MDM remained responsive to opsonised zymosan stimulation, displaying a 3.5-fold elevation in apoE secretion as compared to their non-stimulated counterparts. Cell-associated apoE remained at trace levels under all conditions of cell treatment. Studies involving [35S]methionine incorporation showed de novo synthesis of apoE to be enhanced in both cholesterol-loaded and opsonised-zymosan-stimulated macrophages. Estimation of apoE mRNA in opsonised-zymosan-stimulated and control MDM by dot-blot analysis revealed similar message abundance; by contrast, elevation in cellular cholesterol content following incubation with modified LDL led to a significant increase in apoE mRNA levels. We conclude that the opsonised-zymosan-induced stimulation of apoE synthesis and secretion in human MDM may occur by a mechanism(s) independent of cellular cholesterol content.
Rouis
M
M
Institut National de la Santé et de la Recherche Médicale, Unité 321, Hôpital de la Pitié, Paris, France.
Nigon
F
F
Eggerman
T L
TL
Brewer
H B
HB
Chapman
M J
MJ
D001057:Apolipoproteins E / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D002478:Cells, Cultured; D002784:Cholesterol / Q000494:pharmacology*; D003470:Culture Media; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008970:Molecular Weight; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D015054:Zymosan / Q000494:pharmacology*
D001057:Apolipoproteins E; D003470:Culture Media; D012333:RNA, Messenger; D015054:Zymosan; D002784:Cholesterol