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Published on: September 21, 2021
Lesional accumulation of P2X(4) receptor(+) macrophages in rat CNS during experimental autoimmune encephalomyelitis
1Institute of Brain Research, University of Tuebingen, Calwer Str.3, D-72076 Tuebingen, Germany. lianghao.guo@uni-tuebingen.de
Abstract:
P2X(4) receptor (P2X(4)R) is an ion channel gated by ATP. Here we report the presence and distribution of P2X(4)R by immunohistochemical analysis of the rat CNS. In normal control rats, P2X(4)R was expressed by perivascular cells, but not found on parenchymal monocytic cells. We further investigated P2X(4)R expression in experimental autoimmune encephalomyelitis. P2X(4)R(+) cells were mainly identified as infiltrative macrophages in CNS lesions. In the diseased brain, P2X(4)R(+) leukocytic cells were not only found in the direct vicinity of the inflammatory infiltrate, but widespread distribution was seen in the parenchyma. In experimental autoimmune encephalomyelitis spinal cord, the number of P2X(4)R(+) cells was much higher than in brain. P2X(4)R(+) macrophage accumulation reached the maximal levels around day 14 correlating to the clinical severity of experimental autoimmune encephalomyelitis, and this upregulation lasted until the recovery stage of the disease. This implicates a role of P2X(4)R in the inflammatory process of the CNS. In addition, bromodeoxyuridine immunohistochemistry was employed to demonstrate cell proliferation. Only few bromodeoxyuridine+/P2X(4)R+ monocytes/macrophages were observed in both the diseased brain and spinal cord. In conclusion, this is the first demonstration that P2X(4)R presents in autoimmune-lesioned CNS. Consequently, P2X(4)R might be a valuable marker to dissect the local monocyte heterogeneity in autoimmune disease.
Insights
The P2X(4) receptor (P2X(4)R) is found in the central nervous system (CNS) during autoimmune disease. P2X(4)R is upregulated on macrophages in CNS lesions, suggesting its role in inflammation.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Molecular Neuroscience
Background:
- The P2X(4) receptor (P2X(4)R) is an ATP-gated ion channel.
- Its role in central nervous system (CNS) inflammation is not fully understood.
Purpose of the Study:
- To investigate the presence and distribution of P2X(4)R in the normal and experimentally inflamed rat CNS.
- To determine the cellular identity and dynamics of P2X(4)R-expressing cells during autoimmune neuroinflammation.
Main Methods:
- Immunohistochemical analysis of P2X(4)R expression in rat CNS tissues.
- Experimental autoimmune encephalomyelitis (EAE) model was used to induce CNS inflammation.
- Bromodeoxyuridine (BrdU) immunohistochemistry was employed to assess cell proliferation.
Main Results:
- In normal rats, P2X(4)R was expressed by perivascular cells but not parenchymal monocytes.
- In EAE, P2X(4)R was predominantly found on infiltrative macrophages within CNS lesions.
- P2X(4)R(+) cell accumulation peaked around day 14, correlating with disease severity and persisting into recovery.
- Upregulation of P2X(4)R was more pronounced in the spinal cord compared to the brain.
- Limited co-localization of P2X(4)R with BrdU indicated minimal proliferation of these cells.
Conclusions:
- This study provides the first evidence of P2X(4)R expression in the autoimmune-lesioned CNS.
- P2X(4)R is significantly upregulated on infiltrating macrophages during experimental autoimmune encephalomyelitis.
- P2X(4)R may play a role in the inflammatory processes within the CNS.
- P2X(4)R could serve as a valuable marker for characterizing monocyte/macrophage heterogeneity in autoimmune CNS diseases.
