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Open Access 01-11-2014 | Original Paper

Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients

Authors: Veselin Grozdanov, Corinna Bliederhaeuser, Wolfgang P. Ruf, Valerie Roth, Kathrin Fundel-Clemens, Lisa Zondler, David Brenner, Ana Martin-Villalba, Bastian Hengerer, Jan Kassubek, Albert C. Ludolph, Jochen H. Weishaupt, Karin M. Danzer

Published in: Acta Neuropathologica | Issue 5/2014

Abstract

Despite extensive effort on studying inflammatory processes in the CNS of Parkinson’s disease (PD) patients, implications of peripheral monocytes are still poorly understood. Here, we set out to obtain a comprehensive picture of circulating myeloid cells in PD patients. We applied a human primary monocyte culture system and flow cytometry-based techniques to determine the state of monocytes from PD patients during disease. We found that the classical monocytes are enriched in the blood of PD patients along with an increase in the monocyte-recruiting chemoattractant protein CCL2. Moreover, we found that monocytes from PD patients display a pathological hyperactivity in response to LPS stimulation that correlates with disease severity. Inflammatory pre-conditioning was also reflected on the transcriptome in PD monocytes using next-generation sequencing. Further, we identified the CD95/CD95L as a key regulator for the PD-associated alteration of circulating monocytes. Pharmacological neutralization of CD95L reverses the dysregulation of monocytic subpopulations in favor of non-classical monocytes. Our results suggest that PD monocytes are in an inflammatory predisposition responding with hyperactivation to a “second hit”. These results provide the first direct evidence that circulating human peripheral blood monocytes are altered in terms of their function and composition in PD patients. This study provides insights into monocyte biology in PD and establishes a basis for future studies on peripheral inflammation.

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Title: Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients
Authors: Veselin Grozdanov
Corinna Bliederhaeuser
Wolfgang P. Ruf
Valerie Roth
Kathrin Fundel-Clemens
Lisa Zondler
David Brenner
Ana Martin-Villalba
Bastian Hengerer
Jan Kassubek
Albert C. Ludolph
Jochen H. Weishaupt
Karin M. Danzer
Publication date: 01-11-2014
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 5/2014
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-014-1345-4

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Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients

Abstract

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Springer Medicine

Abstract

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