Expression of myeloid-related protein-8 and-14 in patients with acute Kawasaki disease
Expression of myeloid-related protein-8 and-14 in patients with acute Kawasaki disease
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DOI：
10.1016/j.jacc.2006.02.077
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发表时间：
2006-09-19
影响因子：
24
通讯作者：
Miyawaki, Toshio
中科院分区：
文献类型：
--
作者：
Hirono, Keiich;Foell, Dirk;Miyawaki, Toshio
目的研究急性川崎病(KD)患者血清髓系相关蛋白(MRP)-8/MRP-14作为疾病活动性和冠状动脉病变严重程度的标志物。背景：MRP-8和MRP-14是由活化的中性粒细胞和单核细胞分泌的S100蛋白，可与血管内皮细胞特异性结合，在多种疾病条件下诱导血栓形成和炎症反应。方法观察61例KD患者血清中MRP-8/MRP-14、循环粒细胞和单核细胞中MRP-8和MRP-14信使核糖核酸(MRNA)表达的动态变化结果急性KD早期血清MRP-S/MRP-14水平及粒细胞MRP-8、-14mRNA表达均显著上调，静脉注射免疫球蛋白治疗后24 h内显著下降(P<0.01)；0.05)在45个应答者中。相比之下，在16名无反应者中，这两项指标在最初治疗后都有所增加。急性川崎病患者外周血中MRP-8/MRP-14阳性的循环内皮细胞数量明显高于对照组，发病2周后明显增加，尤以冠状动脉病变患者明显。结论首次发现急性川崎病患者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。血清MR-P-8/MR-P-14水平可能是反映疾病活动性的有用指标，循环内皮细胞MRP-8/MRP-14阳性的水平可预测血管炎的严重程度，证实了在不同的内皮炎症反应中起重要作用。
OBJECTIVES 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.BACKGROUND 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.METHODS 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.RESULTS The serum MRP-S/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.CONCLUSIONS We show for the first time that MRP-8/MRP-14 are exclusively secreted by granulocytes in patients with acute KID, and intravenous immune globulin treatment suppresses their gene expression. Serum levels of MR-P-8/MR-P-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.