[Expression of endothelial nitric oxide synthase and inducible nitric oxide synthase in synovium of rheumatoid arthritis].

Ryumachi. [Rheumatism] Pub Date : 1999-10-01
N Ishiuchi, S Yoshino, M Yokoyama, G Asano
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Abstract

Objectives: To examine the localization and distribution of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), which participate in nitric oxide (NO) production, in synovium of rheumatoid arthritis (RA).

Materials and methods: Immunohistochemical analysis for eNOS and iNOS in synovial tissues obtained from 10 patients with RA who were underwent total knee replacement. Synovial tissues of osteoarthritis (OA) were used as control. The percentage of cells that were positive for eNOS and iNOS was estimated in five hundred endothelial cells, synovial lining cells and interstitial cells, respectively. And mRNA expression of NOS was confirmed by in situ hybridization. In addition, to test NO production, nitration of tyrosines was assessed by immunohistochemistry.

Results: Not only endothelial cells but also synovial lining cells and interstitial cells exhibited immune-reactive both eNOS and iNOS. Cells which were seemed immune-reactive eNOS and iNOS expressed nitrotyrosin. By in situ hybridization, we detected mRNA expression for eNOS and iNOS.

Conclusions: Endothelial cells, synovial lining cells and interstitial cells expressed both eNOS and iNOS with high frequency in RA synovium compared with OA synovium. It seemed to correlate with NO production. These results suggest that expression of iNOS may be involved in the induction of arthritis and eNOS may be participated in augmentation of inflammation in RA.

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类风湿关节炎滑膜内皮型一氧化氮合酶和诱导型一氧化氮合酶的表达。
目的:探讨参与一氧化氮(NO)生成的内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)在类风湿关节炎(RA)滑膜中的定位和分布。材料和方法:对10例接受全膝关节置换术的RA患者滑膜组织的eNOS和iNOS进行免疫组化分析。骨性关节炎(OA)滑膜组织作为对照。分别在500个内皮细胞、滑膜衬里细胞和间质细胞中估计eNOS和iNOS阳性细胞的百分比。原位杂交法检测NOS mRNA表达。此外,通过免疫组织化学评估酪氨酸的硝化作用以检测NO的产生。结果:内皮细胞、滑膜衬里细胞和间质细胞均表现出免疫反应性的eNOS和iNOS。具有免疫反应的eNOS和iNOS细胞表达硝基酪氨酸。通过原位杂交,我们检测了eNOS和iNOS的mRNA表达。结论:RA滑膜内皮细胞、滑膜衬里细胞和间质细胞表达eNOS和iNOS的频率高于OA滑膜。这似乎与一氧化氮的产生有关。这些结果提示,iNOS的表达可能参与关节炎的诱导,eNOS可能参与RA炎症的增强。
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