Title |
Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients
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Published in |
Acta Neuropathologica, October 2014
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DOI | 10.1007/s00401-014-1345-4 |
Pubmed ID | |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Scientists | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 182 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 36 | 20% |
Student > Master | 31 | 17% |
Researcher | 26 | 14% |
Student > Bachelor | 15 | 8% |
Student > Doctoral Student | 10 | 5% |
Other | 24 | 13% |
Unknown | 40 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 39 | 21% |
Biochemistry, Genetics and Molecular Biology | 32 | 18% |
Agricultural and Biological Sciences | 18 | 10% |
Medicine and Dentistry | 18 | 10% |
Immunology and Microbiology | 9 | 5% |
Other | 18 | 10% |
Unknown | 48 | 26% |