Lesional accumulation of P2X(4) receptor(+) macrophages in rat CNS during experimental autoimmune encephalomyelitis.
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.
Guo
L-H
LH
Institute of Brain Research, University of Tuebingen, Calwer Str.3, D-72076 Tuebingen, Germany. lianghao.guo@uni-tuebingen.de
Schluesener
H J
HJ
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002490:Central Nervous System / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D053331:Ectodysplasins; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4; D013997:Time Factors
D015703:Antigens, CD; D016207:Cytokines; D053331:Ectodysplasins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C548228:P2rx4 protein, rat; D016601:RNA-Binding Proteins; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; C077219:small inducible cytokine subfamily E, member 1; D001973:Bromodeoxyuridine