We investigated whether activation of circulating DCs (dendritic cells) or levels of Flt3L (FMS-like tyrosine kinase 3 ligand) and GM-CSF (granulocyte/macrophage colony-stimulating factor), haematopoietic growth factors important for DC differentiation, could account for reduced blood DC numbers in CAD (coronary artery disease) patients. Concentrations of Flt3L and GM-CSF were measured in plasma from CAD patients (n = 15) and controls (n = 12). Frequency and phenotype of mDCs (myeloid dendritic cells) and pDCs (plasmacytoid dendritic cells) were analysed by multicolour flow cytometry in fresh blood, and after overnight incubation with TLR (Toll-like receptor)-4 or -7 ligands LPS (lipopolysaccharide) or IQ (imiquimod). DC function was measured by IL (interleukin)-12 and IFN (interferon)-α secretion. Circulating numbers of CD11c+ mDCs and CD123+ pDCs and frequencies of CD86+ and CCR-7+ (CC chemokine receptor type 7) mDCs, but not pDCs, were declined in CAD. In addition, plasma Flt3L, but not GM-CSF, was lower in patients and positively correlated with blood DC counts. In response to LPS, mDCs up-regulated CD83 and CD86, but CCR-7 expression and IL-12 secretion remained unchanged, similarly in patients and controls. Conversely, pDCs from patients had lower CD83 and CCR-7 expression after overnight incubation and had a weaker IQ-induced up-regulation of CD83 and IFN-α secretion. In conclusion, our results suggest that reduced blood DC counts in CAD are, at least partly, due to impaired DC differentiation from bone marrow progenitors. Decreased levels of mDCs are presumably also explained by activation and subsequent migration to atherosclerotic plaques or lymph nodes. Although mDCs are functioning normally, pDCs from patients appeared to be both numerically and functionally impaired.
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Research Article|
January 18 2011
Decreased numbers of peripheral blood dendritic cells in patients with coronary artery disease are associated with diminished plasma Flt3 ligand levels and impaired plasmacytoid dendritic cell function
Ilse Van Brussel;
*Department of Cardiology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
Correspondence: Ms Ilse Van Brussel (email ilse.van.brussel@uza.be).
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Emily A. Van Vré;
Emily A. Van Vré
*Department of Cardiology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
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Guido R.Y. De Meyer;
Guido R.Y. De Meyer
†Department of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
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Christiaan J. Vrints;
Christiaan J. Vrints
*Department of Cardiology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
‡Division of Cardiology, University Hospital of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium
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Johan M. Bosmans;
Johan M. Bosmans
1
*Department of Cardiology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
‡Division of Cardiology, University Hospital of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium
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Hidde Bult
Hidde Bult
1
†Department of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
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Publisher: Portland Press Ltd
Received:
August 26 2010
Revision Received:
November 10 2010
Accepted:
December 10 2010
Accepted Manuscript online:
December 10 2010
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 120 (9): 415–426.
Article history
Received:
August 26 2010
Revision Received:
November 10 2010
Accepted:
December 10 2010
Accepted Manuscript online:
December 10 2010
Citation
Ilse Van Brussel, Emily A. Van Vré, Guido R.Y. De Meyer, Christiaan J. Vrints, Johan M. Bosmans, Hidde Bult; Decreased numbers of peripheral blood dendritic cells in patients with coronary artery disease are associated with diminished plasma Flt3 ligand levels and impaired plasmacytoid dendritic cell function. Clin Sci (Lond) 1 May 2011; 120 (9): 415–426. doi: https://doi.org/10.1042/CS20100440
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