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

Research output: Journal contributionsJournal articlesResearchpeer-review

Standard

Inhibition of foam cell formation using a soluble CD68-Fc fusion protein. / Daub, Karin; Siegel-Axel, Dorothea ; Schönberger, Tanja et al.
In: Journal of Molecular Medicine, Vol. 88, No. 9, 09.2010, p. 909-920.

Research output: Journal contributionsJournal articlesResearchpeer-review

Harvard

Daub, K, Siegel-Axel, D, Schönberger, T, Leder, C, Seizer, P, Müller, K, Schaller, M, Penz, S, Menzel, D, Buchele, B, Bültmann, A, Münch, G, Lindemann, S, Simmet, T & Gawaz, M 2010, 'Inhibition of foam cell formation using a soluble CD68-Fc fusion protein', Journal of Molecular Medicine, vol. 88, no. 9, pp. 909-920. https://doi.org/10.1007/s00109-010-0629-y

APA

Daub, K., Siegel-Axel, D., Schönberger, T., Leder, C., Seizer, P., Müller, K., Schaller, M., Penz, S., Menzel, D., Buchele, B., Bültmann, A., Münch, G., Lindemann, S., Simmet, T., & Gawaz, M. (2010). Inhibition of foam cell formation using a soluble CD68-Fc fusion protein. Journal of Molecular Medicine, 88(9), 909-920. https://doi.org/10.1007/s00109-010-0629-y

Vancouver

Daub K, Siegel-Axel D, Schönberger T, Leder C, Seizer P, Müller K et al. Inhibition of foam cell formation using a soluble CD68-Fc fusion protein. Journal of Molecular Medicine. 2010 Sept;88(9):909-920. doi: 10.1007/s00109-010-0629-y

Bibtex

@article{c92e86885c2f445bae082e455e0e0f3d,
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.",
keywords = "Chemistry, Atherosclerosis, Foam cells, Lipoproteins, Macrophages, Platelets",
author = "Karin Daub and Dorothea Siegel-Axel and Tanja Sch{\"o}nberger and Christoph Leder and Peter Seizer and Karin M{\"u}ller and Martin Schaller and Susanne Penz and Dirk Menzel and Berthold Buchele and Andreas B{\"u}ltmann and G{\"o}tz M{\"u}nch and Stephan Lindemann and Thomas Simmet and Meinrad Gawaz",
year = "2010",
month = sep,
doi = "10.1007/s00109-010-0629-y",
language = "English",
volume = "88",
pages = "909--920",
journal = "Journal of Molecular Medicine",
issn = "0946-2716",
publisher = "Springer",
number = "9",

}

RIS

TY - JOUR

T1 - Inhibition of foam cell formation using a soluble CD68-Fc fusion protein

AU - Daub, Karin

AU - Siegel-Axel, Dorothea

AU - Schönberger, Tanja

AU - Leder, Christoph

AU - Seizer, Peter

AU - Müller, Karin

AU - Schaller, Martin

AU - Penz, Susanne

AU - Menzel, Dirk

AU - Buchele, Berthold

AU - Bültmann, Andreas

AU - Münch, Götz

AU - Lindemann, Stephan

AU - Simmet, Thomas

AU - Gawaz, Meinrad

PY - 2010/9

Y1 - 2010/9

N2 - 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.

AB - 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.

KW - Chemistry

KW - Atherosclerosis

KW - Foam cells

KW - Lipoproteins

KW - Macrophages

KW - Platelets

UR - http://www.scopus.com/inward/record.url?scp=77956420059&partnerID=8YFLogxK

U2 - 10.1007/s00109-010-0629-y

DO - 10.1007/s00109-010-0629-y

M3 - Journal articles

C2 - 20454888

VL - 88

SP - 909

EP - 920

JO - Journal of Molecular Medicine

JF - Journal of Molecular Medicine

SN - 0946-2716

IS - 9

ER -