Apolipoprotein E expression by human‐monocyte‐derived macrophages

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Abstract
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.