Lesional accumulation of P2X 4 receptor + macrophages in rat CNS during experimental autoimmune encephalomyelitis

Abstract

P2X 4 receptor (P2X 4R) is an ion channel gated by ATP. Here we report the presence and distribution of P2X 4R by immunohistochemical analysis of the rat CNS. In normal control rats, P2X 4R was expressed by perivascular cells, but not found on parenchymal monocytic cells. We further investigated P2X 4R expression in experimental autoimmune encephalomyelitis. P2X 4R + cells were mainly identified as infiltrative macrophages in CNS lesions. In the diseased brain, P2X 4R + 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 4R + cells was much higher than in brain. P2X 4R + 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 4R in the inflammatory process of the CNS. In addition, bromodeoxyuridine immunohistochemistry was employed to demonstrate cell proliferation. Only few bromodeoxyuridine+/P2X 4R+ monocytes/macrophages were observed in both the diseased brain and spinal cord. In conclusion, this is the first demonstration that P2X 4R presents in autoimmune-lesioned CNS. Consequently, P2X 4R might be a valuable marker to dissect the local monocyte heterogeneity in autoimmune disease.