Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease

Jörn F. Dopheide; Viviane Obst; Christopher Doppler; Marie-Christine Radmacher; Martin Scheer; Markus P. Radsak; Tommaso Gori; Ascan Warnholtz; Christian Fottner; Andreas Daiber; Thomas Münzel; Christine Espinola-Klein

doi:10.1160/TH12-05-0327

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2012; 108(06): 1198-1207
DOI: 10.1160/TH12-05-0327

Platelets and Blood Cells

Schattauer GmbH

Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease

Jörn F. Dopheide

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Viviane Obst

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Christopher Doppler

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Marie-Christine Radmacher

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Martin Scheer

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Markus P. Radsak

²Department of Internal Medicine III, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Tommaso Gori

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Ascan Warnholtz

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Christian Fottner

³Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Andreas Daiber

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Thomas Münzel

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

,

Christine Espinola-Klein

¹Department of Internal Medicine II, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

› Institutsangaben

Abstract

Summary

Atherosclerosis is a chronic inflammatory process involving antigen-presenting cells like monocytes and dendritic cells (DC). The aim of this study was to perform a phenotypic characterisation of these cell types in patients with different degrees of peripheral arterial disease (PAD). Sixty patients with PAD [N= 30 intermittent claudication (IC), N= 30 critical limb ischemia (CLI)] and 30 controls were included. Peripheral blood leucocytes were analysed from peripheral blood by flow cytometry using different gating strategies to directly identify and analyse monocytes, myeloid DC, (mDC) and plasmacytoid DC (pDC). PAD patients showed a significantly higher proportion of proinflammatory CD14++CD16+ monocytes (p<0.0001) compared with healthy individuals. We found an increased number of mDC/ml and a reduced number of pDC/ml (both p<0.01) in PAD patients, leading to a shift in the mDC/pDC ratio (p<0.01). As compared to patients with intermittent claudication, CLI patients presented a reduced expression of HLA-DR (p<0.01), CD86 and CD40 on both mDCs and pDCs (p<0.01). Peripheral blood monocytes show a proinflammatory phenotype in PAD patients compared to controls. In contrast, CLI patients show a reduced expression of proinflammatory markers. We hypothesise that severe ischaemia and/or prolonged inflammation in CLI might lead to a paradoxical attenuation in the proinflammatory membrane pattern of circulating mononuclear cells, possibly hindering an adequate regulatory function of mDCs and pDCs and favouring the progression of disease.

Keywords

Monocytes - dendritic cells - inflammation - peripheral arterial disease

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Referenzen

References
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