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

The expression of macrophage scavenger receptors is regulated by intracellu lar cholesterol levels, as well as by cytokines affecting macrophage effect or functions. CD36, a member of the type B scavenger receptor family, will bind a variety of nonlipoprotein and lipoprotein ligands including high-den sity lipoprotein (HDL). Transforming growth factor-beta (TGF-beta) has been demonstrated to modulate macrophage effector functions and is present with in atherosclerotic lesions. In the present study, the effect of TGF-beta on HDL binding by both macrophages and macrophage-derived foam cells was eval uated. TGF-beta, in a dose-dependent manner, reduced the binding of fluroch rome-labeled HDL to both macrophages and foam cells. These effects were obs erved in macrophages derived from nonatherosclerotic (BALB/c) as well as fr om macrophages obtained from both apolipoprotein E and low-density lipoprot ein receptor knockout mice. The decrease in HDL binding was consistent with a significant reduction in CD36 message levels. The effect of TGF-beta on type B scavenger receptor expression was not limited to CD36 as SR-BI messa ge was also downregulated, although the effect was more modest. A similar r eduction in HDL binding and CD36 message was also observed with the immunos uppressive glucocorticoid dexamethasone. These results suggest that within the microenvironment of an atherosclerotic lesion, TGF-beta and other agent s that inhibit macrophage inflammatory responses may impact lesion progress ion through mechanisms that include the modulation of HDL-foam cell interac tions. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.