gms | German Medical Science

24. Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung

Deutsche Gesellschaft für Arterioskleroseforschung

18.03. - 20.03.2010, Blaubeuren

Regulation of OSCAR in endothelial cells by cytokines and growth factors

Meeting Contribution

  • Katharina Nemeth - Institute of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Germany
  • Claudia Göttsch - Medical Clinic III, Dep. of Endocrinology, TU Dresden, Germany
  • Susann Finger - Medical Clinic III, Dep. of Endocrinology, TU Dresden, Germany
  • Lorenz Hofbauer - Medical Clinic III, Dep. of Endocrinology, TU Dresden, Germany
  • Michael Schoppet - Institute of Cardiology, Philipps-University Marburg, Germany
  • corresponding author N. Al-Fakhri - Institute of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Germany

Deutsche Gesellschaft für Arterioskleroseforschung e.V.. 24. Jahrestagung der Deutschen Gesellschaft für Arterioskleroseforschung. Blaubeuren, 18.-20.03.2010. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc10dgaf19

doi: 10.3205/10dgaf19, urn:nbn:de:0183-10dgaf191

Veröffentlicht: 23. März 2011

© 2011 Nemeth et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


The Ig-like osteoclast-associated receptor (OSCAR) has recently been identified as an important co-stimulatory receptor for osteoclast differentiation and cell activation, maturation of macrophages, monocytes, and monocyte-derived dendritic cells.

In this study, we verified the presence of OSCAR in the vascular system and analyzed its protein and mRNA expression in human endothelial cells in response to proinflammatory cytokines and endothelial growth factors to gain insight into its role in the endothelium.


The osteoclast-associated receptor (OSCAR) is a member of the leukocyte receptor complex (LRC)-encoded family of surface receptors. So far, OSCAR was identified and characterized on immune cells [1] and osteoclasts [2]. On immune cells OSCAR plays a role in the cell activation and maturation, in osteoclasts OSCAR is an important costimulatory receptor for cell differentiation. We confirmed the expression of OSCAR on endothelial cells (EC). The aim of this study was to characterize the regulation of OSCAR by endothelial growth factors and inflammatory mediators and to examine its role in the endothelium.


OSCAR was detected on the human endothelial cell line EA.hy926 and on HUVEC by immunofluorescence and Western blot with a monoclonal anti-OSCAR antibody. Furthermore, OSCAR expression on human monocytes and B cells was examined by Western blot. In addition, cell membrane, cytosol and nuclear fractions of HUVECs were prepared with the Subcellular Proteome Extraction Kit ProteoExtract (Calbiochem) and Western blot analysis for OSCAR expression was performed. The human endothelial cell line EA.hy926 was stimulated with 1 ng/ml or 10 ng/ml of the endothelial growth factors VEGF, bFGF and TGF-β. The change of OSCAR expression after 48 h was quantified at the mRNA level with real-time PCR and at the protein level by Western blot. After incubation of EA.hy926 with the proinflammatory cytokines TNF-α (10 ng/ml and 100 ng/ml), INF-α (100 U/ml) and IFN-γ (100 U/ml and 1000 U/ml) for 24 h, protein and mRNA expression of OSCAR were quantified as described above.


Immunofluorescence microscopy and western blot analysis of different cell fractions revealed the localisation of OSCAR on the cell membrane of ECs (Figure 1 [Fig. 1]). OSCAR expression was also detected on monocytes but not on B cells. Incubation of ECs with 10 ng/ml TGF-β for 48 h caused a 3-fold increase of OSCAR mRNA level and a 50% increase in protein expression of OSCAR. VEGF and bFGF and also the lower concentrations of TGF-β (1 ng/ml) had no significant effect on the expression of OSCAR (Figure 2 [Fig. 2]). Incubation with 1000 U/ml of the proinflammatory cytokines TNF-α, INF-α and IFN-γ for 24 h led to a reduction of OSCAR mRNA and protein expression. IFN-γ caused a significant reduction of OSCAR-m-RNA by 62% and the protein concentration was decreased by 44% (Figure 3 [Fig. 3]).


OSCAR is expressed on human ECs and monocytes and it is located on the surface of ECs. OSCAR is therefore presumably, as on immune cells and osteoclasts, a surface receptor with yet unknown ligands. Typical endothelial growth factors such as bFGF and VEGF had no effect on the expression of OSCAR. The increased OSCAR expression caused by TGF-β could, however, point to a role in cell proliferation and differentiation. The down-regulation by proinflammatory cytokines, especially IFN-γ could indicate an immunomodulatory role of OSCAR in ECs. Proinflammatory cytokines in the endothelium modulate costimulatory molecules which influence the T-cell proliferation and thus the immune response [3].

OSCAR could counteract the adhesion or diapedesis of immune cells and would thus be down-regulated for efficient immune response. The exact meaning and mechanisms of this regulation should be explored in further studies of OSCAR by using siRNA knock-down and overexpression.


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