The Cell and Molecular Biology of Apolipoprotein E Synthesis by Macro Phages

Mononuclear phagocytes secrete over 50 different proteins that are regulated during differentiation and that are under the influence of various materials and factors in their extracellular milieu as part of the inflammatory response. The complex nature of the regulation of the expression of these molecules is displayed by apolipoprotein E (ApoE). ApoE mRNA first appears as monocytes differentiate into macrophages, and this expression is paralleled by the secretion of ApoE by the cells. In mature macrophages ApoE synthesis and secretion are decreased by activation of macrophages with endotoxin and interferon-gamma. Although these macrophages contain abundant translatable ApoE mRNA, little ApoE is synthesized, suggesting that this decrease occurs largely at the translational level. ApoE is also controlled at the level of secretion. ApoE is concentrated in the Golgi complex of macrophages and is also found in endoplasmic reticulum, secretion vesicles and coated vesicles. When macrophages come in contact with immune complexes the intracellular ApoE compartment degranulates rapidly. Therefore, ApoE is regulated at the levels of secretion, translation and transcription.