Inhibition of foam cell formation using a soluble CD68-Fc fusion protein

Research output: Journal contributionsJournal articlesResearchpeer-review

Authors

  • Karin Daub
  • Dorothea Siegel-Axel
  • Tanja Schönberger
  • Christoph Leder
  • Peter Seizer
  • Karin Müller
  • Martin Schaller
  • Susanne Penz
  • Dirk Menzel
  • Berthold Buchele
  • Andreas Bültmann
  • Götz Münch
  • Stephan Lindemann
  • Thomas Simmet
  • Meinrad Gawaz

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.

Original languageEnglish
JournalJournal of Molecular Medicine
Volume88
Issue number9
Pages (from-to)909-920
Number of pages12
ISSN0946-2716
DOIs
Publication statusPublished - 09.2010

    Research areas

  • Chemistry
  • Atherosclerosis, Foam cells, Lipoproteins, Macrophages, Platelets