TY - JOUR
T1 - Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions
AU - Liu, Judy S.H.
AU - Zhao, Meng Liang
AU - Brosnan, Celia F.
AU - Lee, Sunhee C.
N1 - Funding Information:
Supported in part by National Multiple Sclerosis Society grant RG 2771 and United States Public Health Service grants NS 11920, NS 31919, and T32GM07288 .
PY - 2001
Y1 - 2001
N2 - Nitric oxide generated by the inducible form of nitric oxide synthase (iNOS) may contribute to the pathogenesis of multiple sclerosis (MS). In this report, we studied postmortem tissues of MS patients for the expression of iNOS by in situ hybridization and immunocytochemistry. Immunocytochemistry for nitrotyrosine, a putative footprint for peroxynitrite formation was also performed. In acute MS lesions, intense reactivity for iNOS mRNA and protein was detected in reactive astrocytes throughout the lesion and in adjacent normal appearing white matter. Staining of macrophages, inflammatory cell infiltrates, and endothelial cells was variable from case to case, but generally detected only in acute lesions. In chronic MS lesions reactive astrocytes at the lesion edge were positive for iNOS whereas the lesion center was nonreactive. Normal appearing white matter demonstrated little reactivity, as did tissues from non-inflamed control brains. Staining for nitrotyrosine was also detected in acute but not chronic MS lesions, and displayed a diffuse parenchymal, membranous, and perivascular pattern of immunoreactivity. These results support the conclusion that iNOS is induced in multiple cell types in MS lesions and that astrocyte-derived nitric oxide could be important in orchestrating inflammatory responses in MS, particularly at the blood-brain barrier.
AB - Nitric oxide generated by the inducible form of nitric oxide synthase (iNOS) may contribute to the pathogenesis of multiple sclerosis (MS). In this report, we studied postmortem tissues of MS patients for the expression of iNOS by in situ hybridization and immunocytochemistry. Immunocytochemistry for nitrotyrosine, a putative footprint for peroxynitrite formation was also performed. In acute MS lesions, intense reactivity for iNOS mRNA and protein was detected in reactive astrocytes throughout the lesion and in adjacent normal appearing white matter. Staining of macrophages, inflammatory cell infiltrates, and endothelial cells was variable from case to case, but generally detected only in acute lesions. In chronic MS lesions reactive astrocytes at the lesion edge were positive for iNOS whereas the lesion center was nonreactive. Normal appearing white matter demonstrated little reactivity, as did tissues from non-inflamed control brains. Staining for nitrotyrosine was also detected in acute but not chronic MS lesions, and displayed a diffuse parenchymal, membranous, and perivascular pattern of immunoreactivity. These results support the conclusion that iNOS is induced in multiple cell types in MS lesions and that astrocyte-derived nitric oxide could be important in orchestrating inflammatory responses in MS, particularly at the blood-brain barrier.
UR - http://www.scopus.com/inward/record.url?scp=0034965383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034965383&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64677-9
DO - 10.1016/S0002-9440(10)64677-9
M3 - Article
C2 - 11395383
AN - SCOPUS:0034965383
SN - 0002-9440
VL - 158
SP - 2057
EP - 2066
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -