Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions

Judy S H Liu, Meng Liang Zhao, Celia F. Brosnan, Sunhee C. Lee

Research output: Contribution to journalArticle

276 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2057-2066
Number of pages10
JournalAmerican Journal of Pathology
Volume158
Issue number6
StatePublished - 2001

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Nitric Oxide Synthase Type II
Multiple Sclerosis
Astrocytes
Nitric Oxide
Immunohistochemistry
Staining and Labeling
Peroxynitrous Acid
3-nitrotyrosine
Blood-Brain Barrier
In Situ Hybridization
Endothelial Cells
Macrophages
Messenger RNA
Brain
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Liu, J. S. H., Zhao, M. L., Brosnan, C. F., & Lee, S. C. (2001). Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. American Journal of Pathology, 158(6), 2057-2066.

Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. / Liu, Judy S H; Zhao, Meng Liang; Brosnan, Celia F.; Lee, Sunhee C.

In: American Journal of Pathology, Vol. 158, No. 6, 2001, p. 2057-2066.

Research output: Contribution to journalArticle

Liu, JSH, Zhao, ML, Brosnan, CF & Lee, SC 2001, 'Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions', American Journal of Pathology, vol. 158, no. 6, pp. 2057-2066.
Liu, Judy S H ; Zhao, Meng Liang ; Brosnan, Celia F. ; Lee, Sunhee C. / Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. In: American Journal of Pathology. 2001 ; Vol. 158, No. 6. pp. 2057-2066.
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