Article
Skewing monocyte polarisation towards protective phenotype in aneurysmal subarachnoid haemorrhage (SAH) – a novel therapeutic approach
Monozyten-Polarisation in den protektiven Phänotyp nach aneurysmatischer Hirnblutung – ein neuer Therapieansatz
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Authors
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Sajjad Muhammad
- Heinrich-Heine-Universität Düsseldorf, Abteilung für Neurochirurgie, Düsseldorf, Deutschland; University of Helsinki, Department of Neurosurgery, Helsinki, Finland; Universitätsklinikum Bonn, Abteilung für Neurochirurgie, Bonn, Deutschland
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Shafqat Rasul Chaudhry
- Universitätsklinikum Bonn, Abteilung für Neurochirurgie, Bonn, Deutschland
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Daniel Hänggi
- Heinrich-Heine-Universität Düsseldorf, Abteilung für Neurochirurgie, Düsseldorf, Deutschland
| Published: | June 26, 2020 |
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Outline
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Objective: State of the art research reveal critical role of inflammation during the phase of early and delayed brain injury after aSAH. Monocytes/macrophages being fundamental part of the innate immunity are the most important players to drive or inhibit inflammation. Monocyte induced inflammation depends on their polarization status either towards M1-type (pro-inflammatory) or M2-type (anti-inflammatory) monocytes. Monocytes polarization and their activation states after aSAH have still not been investigated in detail.
Methods: Peripheral venous blood from 15 SAH patients on day 1 and day 7, and once from 10 healthy controls was used for multicolour flow cytometry. Cells were stained with specific anti-human mouse monoclonal antibodies for 20 minutes and were then acquired on BD LSR FortessaTM. Monocytes were gated based on their intermediate side scatter and CD45 expression. Monocyte subsets were characterized based on differential CD14 and CD16 expression. Activation markers including CCR2, CX3CR1 and HLA-DR were used to quantify activation state of different monocyte subpopulations.
Results: Analysis of monocyte sub-types based on differential CD14 and CD16 expression revealed that non-classical monocytes (M2-type) were significantly decreased compared to healthy controls on day 1. Moreover, intermediate monocytes were significantly higher on post-SAH day 1 compared to day 7. The CX3CR1+ intermediate and non-classical monocytes showed similar significant differences. Intriguingly, classical (M1-type) CCR2+ monocytes significantly increased on post-SAH day 1 as compared to controls and intermediate CCR2+ monocytes compared to post-SAH day 7. Finally, HLA-DR+ expression was impaired on all monocyte sub-population.
Conclusion: Subarachnoid hemorrhage led to increased classical (M1-type) monocytes and decreased alternate (M2-type) monocytes. This imbalance of monocyte polarization towards M1-type cells may exacerbate inflammation mediated post-SAH complication. Skewing monocyte polarization towards M2-type cells after aSAH might be beneficial.
