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Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients
Open accessAbstract
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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“However, it has now been well demonstrated in models of severe trauma or advanced disease states that BM-derived monocytes traffic to and influence inflammatory signaling in the brain (Zhou et al, 2009;Grozdanov et al, 2014).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Grozdanov et al, 2014
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Metadata
- Authors
- Grozdanov, V., Bliederhaeuser, C., Ruf, W. P., Roth, V., Fundel-Clemens, K., Zondler, L., Brenner, D., Martin-Villalba, A., Hengerer, B., Kassubek, J., Ludolph, A. C., Weishaupt, J. H., & Danzer, K. M.
- Affiliations
- Universität Ulm (DE)
- Boehringer Ingelheim (Germany) (DE)
- Corresponding author
- Danzer, Karin M.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2014-10-05
- Volume
- 128
- Issue
- 5
- Pages
- 651-663
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC4201759
- OpenAlex
- W2003612310
- Cited by
- 295
- References
- 44
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 38 · 2023: 23 · 2022: 37 · 2021: 40 · 2020: 26 · 2019: 19 · 2018: 18 · 2017: 18 · 2016: 13 · 2015: 9
- FWCI
- 8.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Fondation Charcot
- Universität Ulm
- Medizinische Fakultät, Universität Ulm
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- Parkinson's disease, peripheral blood monocytes, classical monocytes, MCP-1, lipopolysaccharide response, non-classical monocytes, peripheral inflammation, monocyte transcriptome, disease severity
- MeSH terms
- Cells, Cultured, Culture Media, Female, Flow Cytometry, Humans, Inflammation, Lipopolysaccharides, Male, Monocytes, Parkinson Disease, Phagocytosis, Psychiatric Status Rating Scales, RNA, Messenger, Cohort Studies, Antigens, CD, Interleukin-6, Cytokines, Chemokine CCL2
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