Abstract
The hallmark of the human atherosclerotic plaque is the presence of lipid-laden macrophages, or foam cells. However, many macrophage subsets are found within atherosclerotic lesions and it is not well understood how monocytes differentiate into these subsets. We focused on characterizing macrophages derived in vitro from human peripheral blood monocytes treated with IL-15, IL-4 or IL-10. We show these macrophages to have differing phenotypes: CD209+CD64+, CD209+CD23+, or CD209+CD163+ for macrophages derived from IL-15, IL-4, or IL-10 respectively. To characterize the macrophage subsets ability to become foam cells we measured their uptake of fluorescently-labeled oxidized LDL (oxLDL). IL-10 derived macrophages had the greatest amount of oxLDL uptake. We then investigated the mechanism of uptake and found that fucoidan, a class-A scavenger receptor competitor, significantly inhibited uptake of oxLDL in IL-10 cells. On the other hand a blocking antibody against the class B scavenger receptor, CD36, did not inhibit uptake. Furthermore, we found IL-10 macrophages to express higher mRNA levels of the class A scavenger receptors macrophage receptor with collagenous structure (MARCO) and macrophage scavenger receptor (MSR) expression. These data suggests that IL-10 may promote foam cell formation and is dependent on class-A, but not class B scavenger receptors.
