Cyclooxygenases-1 and -2 are differentially localized to microglia and endothelium in rat EAE and glioma

Cyclooxygenases (COX) mediate a wide variety of derangements observed during diseases of the brain. Their overexpression is involved in the mediation of inflammation, immunomodulation, blood flow, apoptosis and fever. Here, we have analyzed the localization of COX-1 and COX-2 in rat experimental autoimmune encephalomyelitis (EAE), C6 glioblastoma and 9L gliosarcoma by immunohistochemistry. In healthy brain, COX-1 was expressed in single macrophages/microglial cells. Neurons and few endothelial cells expressed COX-2. In EAE, we observed an increase in COX-1+ macrophages/microglial cells and COX-2+ endothelial cells that was closely linked to disease progression. Both COX-1+ macrophages/microglial cells and COX-2+ endothelial cells were abundant in areas of cellular infiltration. In C6 and 9L tumors, high numbers of COX-1+ macrophages/microglial cells and COX-2+ endothelial cells were found both in the tumor parenchyma and in areas of infiltrative tumor growth. Double labeling experiments confirmed expression of COX-2 in vWF+ (endothelial) cells and COX-1 in ED1+ (macophages), OX6+ (MHC class II) and in W3/13+ (lymphoblasts) cells. These data provide further evidence that expression of COX-1 in macrophages/microglial cells and COX-2 in endothelial cells might represent important regulatory mechanisms in inflammatory processes associated with autoimmunity and neoplasia of the rat brain.