Alterations in Blood Monocyte Functions in Parkinson's Disease

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DOI

  • Sara Konstantin Nissen
  • Kalpana Shrivastava, The Lundbeck Foundation Research Center MIND, Department of Biomedicine, Aarhus University, Aarhus, 8000 C, Denmark ; Danish Research Institute of Translational Neuroscience DANDRITE, Aarhus, 8000, Denmark.
  • ,
  • Claudia Schulte, Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, University of Tuebingen & German Center for Neurodegenerative Diseases, Tuebingen, Germany.
  • ,
  • Daniel Erik Otzen
  • David Goldeck, Department of Internal Medicine II, Centre for Medical Research, University of Tuebingen, Tuebingen, Germany.
  • ,
  • Daniela Berg, Department of Neurology, Christian Albrechts University Kiel, Kiel 24104, Germany.
  • ,
  • Holger Jon Møller
  • Walter Maetzler, Department of Neurology, Christian Albrechts University Kiel, Kiel 24104, Germany.
  • ,
  • Marina Romero-Ramos

BACKGROUND: PD is a multisystem disease where both central and peripheral nervous systems are affected. This systemic involvement also includes the immune response in PD, which implicates not only microglia in the brain, but also peripheral immune cells, such as monocytes; however, this aspect has been understudied.

OBJECTIVES: The purpose of this study was to investigate the PD-related changes in peripheral immune cells, their responsiveness to stimulation, and their ability to release immunomodulatory molecules that might have consequences for the disease progression.

METHODS: Using flow cytometry, we investigated the monocytic population in peripheral blood mononuclear cells from PD patients and healthy individuals. We also evaluated the in vitro response to inflammogen lipopolysaccharides and to fibrillar α-synuclein by measuring the expression of CD14, CD163, and HLA-DR and by analysis of soluble immune-related molecules in the supernatant.

RESULTS: Peripheral blood immune cells from PD patients had lower survival in culture, but showed a higher monocytic proliferative ability than control cells, which was correlated with shorter disease duration and late disease onset. In addition, PD patients' cells were less responsive to stimulation, as shown by the lack of changes in CD163 and CD14 expression, and by the absence of significant upregulation of anti-inflammatory cytokines in culture. Moreover, PD peripheral immune cells shed lower in vitro levels of soluble CD163, which suggests a less responsive monocytic population and/or an activation status different from control cells. Interestingly, some of the results were sex associated, supporting a differential immune response in females versus males.

CONCLUSIONS: Our data suggest that PD involves monocytic changes in blood. These cells show reduced viability and are unresponsive to specific stimuli, which might have a relevant consequence for disease progression. © 2019 International Parkinson and Movement Disorder Society.

OriginalsprogEngelsk
TidsskriftMovement Disorders
ISSN0885-3185
DOI
StatusE-pub ahead of print - 26 aug. 2019
Eksternt udgivetJa

Bibliografisk note

© 2019 International Parkinson and Movement Disorder Society.

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