Hirono Keiich, Foell Dirk, Xing Yanlin, Miyagawa-Tomita Sachiko, Ye Fei, Ahlmann Martina, Vogl Thomas, Futatani Takeshi, Rui Chen, Yu Xianyi, Watanabe Kazuhiro, Wanatabe Sayaka, Tsubata Shinichi, Uese Keiichiro, Hashimoto Ikuo, Ichida Fukiko, Nakazawa Makoto, Roth Johannes, Miyawaki Toshio
Department of Pediatrics, Toyama University, Toyama, Japan.
J Am Coll Cardiol. 2006 Sep 19;48(6):1257-64. doi: 10.1016/j.jacc.2006.02.077. Epub 2006 Aug 28.
This study investigated patients with acute Kawasaki disease (KD) to validate myeloid-related protein (MRP)-8/MRP-14 as a marker of disease activity and severity of coronary artery lesion development.
Both MRP-8 and -14, which are S100-proteins secreted by activated neutrophils and monocytes, bind specifically to endothelial cells and induce thrombogenic and inflammatory responses in a variety of disease conditions.
We investigated 61 patients with acute KD and examined sequential changes in serum levels of MRP-8/MRP-14, messenger ribonucleic acid (mRNA) expression of MRP-8 and -14 in circulating granulocytes and monocytes, and amounts of MRP-8/MRP-14 bound to circulating endothelial cells.
The serum MRP-8/MRP-14 levels as well as mRNA expressions of MRP-8 and -14 in granulocytes were strongly upregulated during the early stage of acute KD, and decreased dramatically within 24 h of intravenous immune globulin therapy (p < 0.05) in 45 responders. In contrast, in 16 nonresponders both of these increased after the initial treatment. The number of MRP-8/MRP-14-positive circulating endothelial cells was higher in patients with acute KD than in control patients and increased significantly by 2 weeks after the onset of KD, especially in patients in whom coronary artery lesions developed.
We show for the first time that MRP-8/MRP-14 are exclusively secreted by granulocytes in patients with acute KD, and intravenous immune globulin treatment suppresses their gene expression. Serum levels of MRP-8/MRP-14 may be useful markers of disease activity, and the levels of MRP-8/MRP-14-positive circulating endothelial cell may predict the severity of vasculitis, confirming an important role for distinct inflammatory reactions in endothelium.
本研究对急性川崎病（KD）患者进行调查，以验证髓样相关蛋白（MRP）-8/MRP-14作为疾病活动度及冠状动脉病变发展严重程度的标志物。
MRP-8和-14均为活化的中性粒细胞和单核细胞分泌的S100蛋白，在多种疾病状态下可特异性结合内皮细胞并诱导血栓形成和炎症反应。
我们对61例急性KD患者进行了研究，检测了MRP-8/MRP-14的血清水平、循环粒细胞和单核细胞中MRP-8和-14的信使核糖核酸（mRNA）表达，以及与循环内皮细胞结合的MRP-8/MRP-14的量的连续变化。
急性KD早期，血清MRP-8/MRP-14水平以及粒细胞中MRP-8和-14的mRNA表达均显著上调，45例有反应者在静脉注射免疫球蛋白治疗24小时内显著下降（p<0.05）。相比之下，16例无反应者在初始治疗后两者均升高。急性KD患者中MRP-8/MRP-14阳性循环内皮细胞的数量高于对照患者，且在KD发病后2周显著增加，尤其是发生冠状动脉病变的患者。
我们首次表明，急性KD患者中MRP-8/MRP-14仅由粒细胞分泌，静脉注射免疫球蛋白治疗可抑制其基因表达。MRP-8/MRP-14的血清水平可能是疾病活动度的有用标志物，MRP-8/MRP-14阳性循环内皮细胞的水平可能预测血管炎的严重程度，证实了内皮细胞中不同炎症反应的重要作用。
