J Neuroimmunol. 2004 Apr;149(1-2):40-9
Rose JW, Hill KE, Watt HE, Carlson NG.
Neurovirology Research Laboratory VASLCHCS, 500 Foothill Dr. Salt Lake City, UT 84148, USA
Multiple sclerosis (MS) is a progressive immune-mediated disease characterized by the loss of the oligodendrocytes that constitute the myelin sheath.
Recent reports show that glutamate-mediated excitotoxic death of oligodendrocytes contributes to pathogenesis in demyelinating disease.
A link between the immune-mediated inflammatory response and glutamate-mediated excitotoxicity of oligodendrocytes could involve the interaction of inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2).
Both enzymes are tightly coupled to neuronal excitotoxic death.
We examined tissue from two controls and seven MS patients with chronic active lesions to determine the extent of COX-2 and iNOS expression.
In contrast to the lack of expression in controls, there was a marked induction of COX-2 in all these MS lesions.
COX-2 was frequently expressed in association with iNOS.
COX-2 was found in areas that contained catabolites of myelin basic protein, indicating recent demyelination.
COX-2 expression was found near damaged oligodendrocytes in cells that expressed the macrophage/microglia marker CD64, indicating that a substantial portion of the COX-2 in the lesions was expressed in immune-derived cells.
We discuss these findings in the context of how COX-2 could be coupled with iNOS to contribute to excitotoxic death and damage of oligodendrocytes.