title: Inhibition of foam cell formation using a soluble CD68-Fc fusion protein.
abstract: The appearance of lipid-rich foam cells is a major feature of vulnerable atherosclerotic plaque formation. The transformation of macrophages into foam cells results from excessive uptake of cholesterol-rich particles by scavenger receptors such as CD68. We cloned a CD68-Fc immunoadhesin, a fusion protein consisting of the extracellular domain of the human CD68 and a human Fc domain, and investigated the function in vitro. Specific binding of CD68-Fc to OxLDL with an affinity of 10 nmol/L was determined by surface plasmon resonance and increased binding to lipid-rich human and ApoE(-/-) mice plaque tissue. This was confirmed both by immunohistochemical staining of CD68-Fc-treated paraffin sections from human plaques and by ELISA-based quantification of CD68-Fc binding to human atherosclerotic plaque extracts. In an in vitro model of macrophage/foam cell formation, CD68-Fc reduced foam cell formation significantly. This was caused both by interference of CD68-Fc with OxLDL uptake into macrophages and platelets and by the inhibition of platelet/OxLDL phagocytosis. Finally, expression of metalloproteinases by macrophages/foam cells was inhibited by CD68-Fc. In conclusion, CD68-Fc seems to be a promising new tool for preventing macrophage/foam cell formation. Thus, CD68-Fc might offer a novel therapeutic strategy for patients with acute coronary syndrome by modulating the generation of vulnerable plaques.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universität Tübingen, Otfried-Müller Str.10, 72076 Tübingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Daub
authors.forename: Dorothea
authors.initials: D
authors.lastname: Siegel-Axel
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Christoph
authors.initials: C
authors.lastname: Leder
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.forename: Karin
authors.initials: K
authors.lastname: Müller
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Sandra
authors.initials: S
authors.lastname: Penz
authors.forename: Dagmar
authors.initials: D
authors.lastname: Menzel
authors.forename: Berthold
authors.initials: B
authors.lastname: Büchele
authors.forename: Andreas
authors.initials: A
authors.lastname: Bültmann
authors.forename: Götz
authors.initials: G
authors.lastname: Münch
authors.forename: Stephan
authors.initials: S
authors.lastname: Lindemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmet
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005487:Foam Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000235:genetics; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020349:Surface Plasmon Resonance; D014162:Transfection; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D007141:Immunoglobulin Fc Fragments; D008077:Lipoproteins, LDL; D051116:Receptors, Scavenger; D011993:Recombinant Fusion Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C099252:oxidized low density lipoprotein
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