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 H2O2.
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 H2O2 secretion by macrophages. In contrast, macrophages adherent to surfaces coated with oxLDL secreted three- to fourfold more H2O2 than macrophages adherent to surfaces coated with acLDL or native LDL. Freshly isolated blood monocytes secreted little H2O2 regardless of the substrate on which they were plated. H2O2 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 H2O2 secretion by these cells. These studies show that MSR-A is primarily 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 H2O2 secretion by macrophages.
Maxeiner
H
H
Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Husemann
J
J
Thomas
C A
CA
Loike
J D
JD
El Khoury
J
J
Silverstein
S C
SC
D000107:Acetylation; D000911:Antibodies, Monoclonal; D018955:CD36 Antigens / Q000276:immunology / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes; D010084:Oxidation-Reduction / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D012603:Scopoletin / Q000378:metabolism; D012995:Solubility
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C495139:MSR1 protein, human; D011134:Polysaccharides; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; C099252:oxidized low density lipoprotein; C007789:fucoidan; D006861:Hydrogen Peroxide; D002374:Catalase; D012603:Scopoletin