Complementary Roles for Scavenger Receptor A and CD36 of Human Monocyte–derived Macrophages in Adhesion to Surfaces Coated with Oxidized Low-Density Lipoproteins and in Secretion of H(2)O(2)

Oxidized low-density lipoprotein (oxLDL) is considered one of the principal effectors of atherogenesis. To explore mechanisms by which oxLDL affects human mononuclear phagocytes, we incubated these cells in medium containing oxLDL, acetylated LDL (acLDL), or native LDL, or on surfaces coated with these native and modified lipoproteins. The presence of soluble oxLDL, acLDL, or native LDL in the medium did not stimulate H(2)O(2) secretion by macrophages. In contrast, macrophages adherent to surfaces coated with oxLDL secreted three- to fourfold more H(2)O(2) than macrophages adherent to surfaces coated with acLDL or native LDL. Freshly isolated blood monocytes secreted little H(2)O(2) regardless of the substrate on which they were plated. H(2)O(2) secretion was maximal in cells maintained for 4–6 d in culture before plating on oxLDL-coated surfaces. Fucoidan, a known ligand of class A macrophage scavenger receptors (MSR-A), significantly reduced macrophage adhesion to surfaces coated with oxLDL or acLDL. Monoclonal antibody SMO, which blocks oxLDL binding to CD36, did not inhibit adhesion of macrophages to oxLDL-coated surfaces but markedly reduced H(2)O(2) secretion by these cells. These studies show that MSR-A is primarily responsible for adhesion of macrophages to oxLDL-coated surfaces, that CD36 signals H(2)O(2) secretion by macrophages adherent to these surfaces, and that substrate-bound, but not soluble, oxLDL stimulates H(2)O(2) secretion by macrophages.