title: The pivotal role of scavenger receptor CD36 and phagocyte-derived oxidants in oxidized low density lipoprotein-induced adhesion to endothelial cells.
abstract: Adhesion of phagocytes to endothelial cells constitutes a crucial step in atherogenesis. Oxidized low density lipoproteins (LDL) are supposed to facilitate the adhesion process. We investigated the molecular mechanisms by which mildly and extensively hypochlorite-oxidized LDL force adhesion of murine macrophages and human neutrophils to human umbilical venous endothelial cells. After 1h of co-incubation of macrophages, endothelial cells, and lipoproteins adhesion significantly increased to 160+/-13% (S.E.M., n=5) in the presence of mildly oxidized lipoprotein, and 210+/-11% (S.E.M., n=5) in the presence of extensively oxidized lipoprotein. Similar results were obtained with neutrophils. CD36 antibody (FA6-152) significantly reduced adhesion to 102+/-7% (S.E.M., n=5) using mildly oxidized low density lipoprotein and to 179+/-16% (S.E.M., n=5) using extensively oxidized low density lipoprotein. Native high density lipoprotein and to a lesser extent methionine-oxidized high density lipoprotein significantly counteracted the effects of low density lipoprotein. Prior incubation of endothelial cells with modified lipoproteins followed by their removal and subsequent incubation with macrophages or neutrophils resulted in only minor changes of adhesion. This suggests that the direct contact of low density lipoprotein with phagocytes followed by activation of a respiratory burst with release of reactive oxygen species facilitates the adhesion process. Accordingly, the addition of antioxidants (superoxide dismutase and catalase) to the co-incubation medium was followed by a significant decrease in phagocyte adhesion. It is concluded that oxidized low density lipoprotein-induced respiratory burst activation of phagocytes with subsequent release of oxidants constitutes a crucial step in promoting the adhesion of phagocytes to endothelial cells.
authors.affiliation: Department of Internal Medicine 3, Carl Gustav Carus Medical School, University of Technology Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany. steffi.kopprasch@mailbox.tu-dresden.de
authors.forename: Steffi
authors.initials: S
authors.lastname: Kopprasch
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Westendorf
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Kruse
authors.forename: Jürgen
authors.initials: J
authors.lastname: Grässler
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL / Q000737:chemistry; D008262:Macrophage Activation; D051379:Mice; D016877:Oxidants / Q000378:metabolism*; D010084:Oxidation-Reduction; D010586:Phagocytes / Q000187:drug effects / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins
chemical_list: D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D016877:Oxidants; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; C099252:oxidized low density lipoprotein; D006997:Hypochlorous Acid