Yu Xianyi, Hirono Kei-Ich, Ichida Fukiko, Uese Kei-Ichiro, Rui Chen, Watanabe Sayaka, Watanabe Kazuhiro, Hashimoto Ikuo, Kumada Tokimasa, Okada Eikichi, Terai Masaru, Suzuki Atsuko, Miyawaki Toshio
Department of Pediatrics, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama, 930-0194 Japan.
Pediatr Res. 2004 Apr;55(4):688-94. doi: 10.1203/01.PDR.0000113464.93042.A4. Epub 2004 Feb 5.
Nitric oxide (NO) serves many vasoprotective roles, but the massive release of NO causes arterial wall degeneration. We investigated whether enhanced nitric oxide synthase (iNOS) expression in peripheral blood leukocytes and circulating endothelial cells mirrors the progression of coronary arterial lesions in 55 children with acute Kawasaki disease (KD), including 24 with and 31 without coronary artery lesions (CAL). Patients were treated with i.v. gamma-globulin at the time of diagnosis and blood samples were collected before and after treatment. The cellular origin of NO synthesis was determined by flow cytometric analysis of iNOS expression in peripheral blood, and by immunohistochemical analysis of circulating endothelial cells and coronary arteries. iNOS expression in neutrophils peaked at the time of diagnosis, but did not peak in monocytes until 2 wk post onset of disease. Levels were significantly higher in both cell types in patients with CAL (p = 0.001 and p = 0.035, respectively). In addition, the number of circulating endothelial cells and levels of iNOS expression were higher in patients with CAL (p = 0.011 and p = 0.012, respectively). Immunohistochemical analysis of the coronary arteries from three patients with acute KD revealed iNOS immunoreactivity in endothelial cells, as well as infiltrating monocytes/macrophages in the aneurysms. We conclude that the expression of iNOS in peripheral blood leukocytes, as well as circulating endothelial cells, correlates with the severity of coronary arterial wall injury and the progression of CAL in patients with acute KD.
一氧化氮（NO）具有多种血管保护作用，但大量释放的NO会导致动脉壁变性。我们调查了55例急性川崎病（KD）患儿外周血白细胞和循环内皮细胞中一氧化氮合酶（iNOS）表达增强是否反映冠状动脉病变的进展，其中24例有冠状动脉病变（CAL），31例无冠状动脉病变。患者在诊断时接受静脉注射丙种球蛋白治疗，并在治疗前后采集血样。通过对外周血中iNOS表达的流式细胞术分析以及对循环内皮细胞和冠状动脉的免疫组织化学分析来确定NO合成的细胞来源。中性粒细胞中的iNOS表达在诊断时达到峰值，但单核细胞中的iNOS表达直到疾病发作后2周才达到峰值。CAL患者这两种细胞类型中的水平均显著更高（分别为p = 0.001和p = 0.035）。此外，CAL患者的循环内皮细胞数量和iNOS表达水平更高（分别为p = 0.011和p = 0.012）。对3例急性KD患者的冠状动脉进行免疫组织化学分析发现，内皮细胞以及动脉瘤中浸润的单核细胞/巨噬细胞中有iNOS免疫反应性。我们得出结论，外周血白细胞以及循环内皮细胞中iNOS的表达与急性KD患者冠状动脉壁损伤的严重程度和CAL的进展相关。
