TGF-β reduced binding of high-density lipoproteins in murine macrophages and macrophage-derived foam cells

The expression of macrophage scavenger receptors is regulated by intracellular cholesterol levels, as well as by cytokines affecting macrophage effector functions. CD36, a member of the type B scavenger receptor family, will bind a variety of nonlipoprotein and lipoprotein ligands including high-density lipoprotein (HDL). Transforming growth factor-β (TGF-β) has been demonstrated to modulate macrophage effector functions and is present within atherosclerotic lesions. In the present study, the effect of TGF-β on HDL binding by both macrophages and macrophage-derived foam cells was evaluated. TGF-β, in a dose-dependent manner, reduced the binding of flurochrome-labeled HDL to both macrophages and foam cells. These effects were observed in macrophages derived from nonatherosclerotic (BALB/c) as well as from macrophages obtained from both apolipoprotein E and low-density lipoprotein receptor knockout mice. The decrease in HDL binding was consistent with a significant reduction in CD36 message levels. The effect of TGF-β on type B scavenger receptor expression was not limited to CD36 as SR-BI message was also downregulated, although the effect was more modest. A similar reduction in HDL binding and CD36 message was also observed with the immunosuppressive glucocorticoid dexamethasone. These results suggest that within the microenvironment of an atherosclerotic lesion, TGF-β and other agents that inhibit macrophage inflammatory responses may impact lesion progression through mechanisms that include the modulation of HDL–foam cell interactions.