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What effect do immigrant macrophages have after a stroke?
In the event of a stroke, the brain tissue is damaged and, in the event of survival, the body then shows various other reactions that have so far been poorly understood. A recent study has now made it clear that so-called macrophages from the bone marrow migrate into the brain after a stroke. The researchers have also tried to decipher the effect of the giant phagocytes there.
A research team from the Jena University Hospital, the University of Bonn and the Memorial Sloan Kettering Cancer Center in New York (USA) has used a new method to demonstrate that macrophages from the bone marrow migrate into the brain after a stroke. The researchers also examined the effect of the immigrant giant phagocytes in the mouse model. Their results were published in the renowned journal "Nature Neuroscience".
Crucial for brain development and function
As components of the innate immune system, macrophages can be found in every tissue in our body and the giant phagocytes are also of crucial importance for brain development and function, the researchers explain. The immune cells located there are called microglia.
Recruited macrophages from the bone marrow
However, "during inflammatory processes, for example after a stroke, brain infections, multiple sclerosis or Alzheimer's disease, other macrophages come into play that are recruited from the bone marrow," the research team continues.
Here the researchers asked themselves to what extent it makes a difference with regard to brain diseases, whether the macrophages are resident in the brain or have immigrated to the brain. Since the two cell types could not be distinguished from one another using conventional means, this had not been ascertainable until now.
Immigrated macrophages after a stroke
However, the research team has now developed a new method with which they can illuminate macrophages that have been formed in the bone marrow. Using this technology, they were able to demonstrate in studies on mice that "shortly after a stroke, numerous macrophages that had migrated from the blood attack dead and adjacent healthy brain tissue."
“The team examined mice in which the genetic information for a molecular switch was inserted into a gene called Cxcr4. If you activate this switch with a special active ingredient, stem cells in the bone marrow, from which all of the immune cells circulating in the blood originate, will henceforth produce a colored fluorescent protein, ”according to the Jena University Hospital.
No immigrant macrophages in healthy mice
Since the glow only passes on to the daughter cells circulating in the blood, while resident microglia are not marked in the brain, the researchers were able to differentiate the immigrant immune cells by their color from microglia. In this way, it was possible to demonstrate "that practically no macrophages formed by bone marrow stem cells settle in the brain during a healthy mouse life."
Giant phagocytes withdrew again
The research team led by Professor Dr. Ralf Stumm from Jena University Hospital, Professor Dr. Elvira Mass from the University of Bonn and Professor Dr. According to Frederic Geissmann from the Memorial Sloan Kettering Cancer Center in New York, the studies also found that the immigrant giant phagocytes completely withdrew from the healthy brain tissue in the following days and were then only found in the dead brain tissue.
Special gene function of crucial importance
For further investigations, the researchers inactivated a special gene function (Cxcr4 gene function), which plays an essential role in inflammatory processes in the brain. In the absence of Cxcr4 function, fewer macrophages were attracted to the brain after a stroke, and the immigrant macrophages withdrew only incompletely into the dead brain tissue in the following days, reports the research team.
In addition, when the Cxcr4 gene function was inactive, "numerous genes that are necessary for a protective immune response were not switched on in the immigrated macrophages, whereas inflammation-promoting genes were too strongly developed in the resident macrophages," says Prof. Elvira Mass. Also, some macrophages remained in healthy brain tissue for far too long and prevented microglia residing there from resting.
Recruited macrophages protect the brain
Overall, the lack of the Cxcr4 receptor in mice with a stroke resulted in slightly increased tissue damage and a poorer overall condition of the mice, the research team continued. The study results make it clear "that the Cxcr4 receptor is part of an immune response with which macrophages from bone marrow protect the damaged brain."
The better the spatial and temporal activation of the Cxcr4 molecule is understood during a stroke, the better it will be possible to help with Cxcr4-inhibiting drugs in the future, emphasizes Prof. Stumm.
Universal tool for further research
According to the researchers, an important milestone is the discovered genetic switch with which they illuminated the macrophages from the bone marrow. This is a universal tool with which the function of the immune cells originating from the bone marrow can be better examined in the future. (fp)
Author and source information
This text corresponds to the specifications of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
Dipl. Geogr. Fabian Peters
- Jena University Hospital: Stroke: Macrophages migrate from the blood (published February 11, 2020), uniklinikum-jena.de
- Yves Werner, Elvira Mass, Praveen Ashok Kumar, Thomas Ulas, Kristian Handel, Arik Horne, Kathrin Klee, Amelie Lupp, Dagmar Schütz, Friederike Saaber, Christoph Redecker, Joachim L. Schultze, Frederic Geissmann, Ralf Stumm: Cxcr4 distinguishes HSC-derived monocytes from microglia and reveals monocyte immune responses to experimental stroke; in Natur Neuroscience (published 02/10/2020), nature.com