Department of Dermatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan ; Brain Science Institute, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno, Osaka 545-8585, Japan.
J Clin Biochem Nutr. 2013 Jan;52(1):17-21. doi: 10.3164/jcbn.12-52. Epub 2012 Oct 24.
To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO-synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we analyzed changes in the frequency of sneezing, plasma levels of NO metabolites, α-melanocyte-stimulating hormone (MSH) and immunoglobulin E and tracheal expression of IgA and mast cell tryptase in control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized with Cry j I antigen. After the last intranasal challenge of antigen, changes in the frequency of sneezing and plasma levels of IgE, α-MSH and NO metabolites and tracheal expression of iNOS, IgA and mast cell tryptase were analyzed by ELISA and immunohistochemistry using specific antibodies. The sensitization of mice with Cry j I antigen increased plasma levels of NO metabolites, α-MSH and IgE and tracheal expression of iNOS, IgA and mast cell tryptase in control not but in iNOS(-/-) mice. Administration of N(G)-nitro-L-arginine methyl ester strongly inhibited all these changes occurred in control mice. These results indicate that the symptom of pollinosis including sneezing is enhanced by iNOS derived NO through activation of α-MSH-receptor containing mast cells enriched with tryptase.
为了阐明诱导型一氧化氮合酶 (iNOS) 产生的一氧化氮 (NO) 可能参与变应性鼻炎的发病机制,我们分析了打喷嚏频率、NO 代谢产物、α-黑素细胞刺激素 (MSH) 和免疫球蛋白 E 血浆水平以及 IgA 和肥大细胞胰蛋白酶在对照和 iNOS(-/-) 小鼠气管中的表达变化。8 周龄的对照和 iNOS(-/-) 雄性 C57BL/6j 小鼠用 Cry j I 抗原致敏。在最后一次鼻内抗原挑战后,通过 ELISA 和免疫组织化学使用特异性抗体分析打喷嚏频率和 IgE、α-MSH 和 NO 代谢产物以及 iNOS、IgA 和肥大细胞胰蛋白酶在气管中的表达变化。Cry j I 抗原致敏的小鼠增加了对照小鼠而不是 iNOS(-/-) 小鼠的 NO 代谢产物、α-MSH 和 IgE 血浆水平以及 iNOS、IgA 和肥大细胞胰蛋白酶的气管表达。N(G)-硝基-L-精氨酸甲酯的给药强烈抑制了对照小鼠中发生的所有这些变化。这些结果表明,打喷嚏等花粉症症状通过激活富含胰蛋白酶的含有 α-MSH 受体的肥大细胞产生的 iNOS 衍生的 NO 而增强。