Blood Monocyte Functions Altered in Parkinson's Disease

Parkinson's disease is characterized by the slow degeneration of the neurons in brain due to the abnormal accumulation of a protein called alpha-synuclein. This leads to the patients shaking and then to the slow, stiff movements which many people associate with the disease.

Parkinson's disease (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.

Biomedical scientists at Aarhus University (Aarhus, Denmark) and their colleagues included in their cross-sectional study 29 Parkinson's patients and 20 healthy control subjects of the same age and gender distribution. 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.

The team used flow cytometry on a NovoCyte FACS machine to investigate the monocytic population in peripheral blood mononuclear cells from PD patients and healthy individuals. They 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. These markers were subsequently measured on the cell surface using flow cytometry and on secreted cytokines using enzyme-linked immunosorbent assay (ELISA) and Meso Scale Instrumentation.

The scientists reported that 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.

Sara Konstantin Nissen, PhD, the lead author of the study, said, “The immune system functions in a delicate balance. On the one hand, it cleans up invasive microorganisms and accumulations of unwanted proteins, such as alpha-synuclein, and does so by creating an inflammatory condition. But on the other hand, the immune system must also avoid damaging the body's own cells via too much inflammation, and apparently this balance goes awry in the case of Parkinson's disease.” The study was first published online on August 26, 2019, in the journal Movement Disorders.

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