Restricted cyclooxygenase-2 expression in the central nervous system following acute and delayed-type hypersensitivity responses to bacillus Calmette-Guérin.
The expression of cyclooxygenase-2, a key enzyme in prostaglandin and thromboxane synthesis in inflammation, was studied immunohistochemically in in vivo models of acute and chronic inflammatory responses in rat central nervous system. In the acute inflammatory response to intracranial injection of heat-killed bacillus Calmette-Guérin as well as in the immune-mediated, delayed-type hypersensitivity response to the same pathogen, cyclooxygenase-2 expression was restricted to major infiltrating haematogenous cell populations such as neutrophils and mononuclear phagocytes, while the expression of the enzyme by brain non-neuronal resident cells (astrocytes, microglia, perivascular cells) appeared to be limited to perivascular cells of the blood vessels in the vicinity of the lesion and in the surrounding area. On the basis of their morphology and location, these perivascular cells were identified as perivascular macrophages, but we could not rule out the possibility that some endothelial cells also expressed cyclooxygenase-2. The constitutive neuronal cyclooxygenase-2 was not affected by the ongoing inflammation. Interestingly, in spite of the extensive astrocyte and microglial reaction occurring over a broad area surrounding the inflammatory lesions, there was no obvious cyclooxygenase-2 staining in these cells. These data indicate that the up-regulation of cyclooxygenase-2 expression in acute and chronic, immune-mediated lesions in the brain parenchyma is remarkably restricted to the lesion site. Since cyclooxygenase metabolites can regulate important functions of resident as well as infiltrating cells, the increased synthesis of prostaglandins and thromboxanes, which is likely to occur as a consequence of the expression of cycloxygenase-2 at the lesion site, might represent an important component of the inflammatory processes within the brain.
Minghetti
L
L
Laboratory of Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
Hughes
P
P
Perry
V H
VH
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000276:immunology; D002490:Central Nervous System / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D006968:Hypersensitivity, Delayed / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006969:Hypersensitivity, Immediate / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D009163:Mycobacterium bovis / Q000276:immunology*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases