Complementary roles for scavenger receptor A and CD36 of human monocyte-derived macro-phages in adhesion to surfaces coated with oxidized low-densitylipoproteins and in secretion of H2O2

Oxidized low-density lipoprotein (oxLDL) is considered one of the principal effectors of atherogenesis. To explore mechanisms by which oxLDL affects h uman mononuclear phagocytes, we incubated these cells in medium containing oxLDL, acetylated LDL (acLDL), or native LDL, or on surfaces coated with th ese native and modified lipoproteins. The presence of soluble oxLDL, acLDL, or native LDL in the medium did not stimulate H2O2 secretion by macrophage s. In contrast, macrophages adherent to surfaces coated with acLDL or nativ e LDL. Freshly isolated blood monocytes secreted little H2O2 regardless of the substrated on which they were plated. H2O2 secretion was maximal in cel ls 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 o r acLDL. Monoclonal antibody SMO, which blocks oxLDL binding to CD36, did n ot inhibit adhesion of macrophages of oxLDL-coated surfaces but markedly re duced H2O2 secretion by these cells. These studies show that MSR-A is prima rily responsible for adhesion of macrophages to oxLDL-coated surfaces, that CD36 signals H2O2 secretion by macrophages adherent to these surfaces, and that substrate-bound, but not soluble, oxLDL stimulates H(2)O(2 )secretion by macrophages.