Endocytosis of oxidized LDL and reversibility of migration inhibition in macrophage-derived foam cells in vitro. A mechanism for atherosclerosis regression?

Abstract

The ability of macrophage-derived foam cells to migrate from atherosclerotic lesions represents one potential mechanism for the regression of atherosclerosis. It is, however, generally recognized that the transformation of macrophages into foam cells results in greatly reduced migrational ability. In the present study, we set out to investigate the factors affecting migratory capability in foam cell-like cells with the use of an in vitro assay. Foam cell-like cells were prepared by incubating macrophages in the presence of oxidized low density lipoprotein (LDL). The transformation to a typical foam cell morphology was demonstrated by Nile red staining (light microscopy), and the mechanisms of binding, uptake, and intracellular processing of oxidized LDL were established by colloidal gold labeling on the ultrastructural level. With the in vitro assay, the migration of these foam cell-like cells was found to be markedly inhibited compared with untreated, control macrophages. However, zymosan-activated mouse serum restored migration in oxidized LDL-treated cells to levels similar to those of control cells. Restoration of migratory capacity was accompanied by alterations in the cytoskeleton system, especially in actin arrangement.