Synthesis of Apolipoprotein A-I in Human Macrophages Enhances their Migratory Activity.

Apolipoprotein A-I (ApoA-I) is the major structural and functional protein of high density lipoprotein (HDL) particles. ApoA-I has antioxidant, anti-inflammatory and atheroprotective properties. Although the main sites of ApoA-I synthesis in humans are liver and small intestine, ApoA-I expression was also found in monocytes and macrophages. In the present study we demonstrate the involvement of ApoA-I, synthesized by macrophages, in the regulation of migratory activity of these cells induced by C5a. ApoA-I in macrophages enhances migration of these cells via ABCA1-independent mechanism. Exogenous and endogenous (synthesized by macrophages) ApoA-I have the different effects on the macrophage migration, activating the different targets. We have revealed the mechanism of ApoA-I-dependent stimulation of macrophage chemotaxis: endogenous ApoA-I decreases the synthesis and secretion of netrin-1 (an inhibitor of macrophage emigration from the atherosclerotic plaque into the lymph nodes) and also downregulates its receptor UNC5B. Moreover, the incubation of macrophages with netrin-1 reduced mRNA and membrane-associated levels of ApoA-I, that proved the existence of negative feedback loop between netrin-1 and ApoA-I in macrophages.