TY - JOUR
T1 - Expression of Myeloid-Related Protein-8 and -14 in Patients With Acute Kawasaki Disease
AU - Hirono, Keiich
AU - Foell, Dirk
AU - Xing, Yanlin
AU - Miyagawa-Tomita, Sachiko
AU - Ye, Fei
AU - Ahlmann, Martina
AU - Vogl, Thomas
AU - Futatani, Takeshi
AU - Rui, Chen
AU - Yu, Xianyi
AU - Watanabe, Kazuhiro
AU - Wanatabe, Sayaka
AU - Tsubata, Shinichi
AU - Uese, Keiichiro
AU - Hashimoto, Ikuo
AU - Ichida, Fukiko
AU - Nakazawa, Makoto
AU - Roth, Johannes
AU - Miyawaki, Toshio
N1 - Funding Information:
This study was supported by grants from the Japan Kawasaki Disease Research Center.
PY - 2006/9/19
Y1 - 2006/9/19
N2 - 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-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. Conclusions: 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.
AB - 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-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. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=33748437572&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2006.02.077
DO - 10.1016/j.jacc.2006.02.077
M3 - 学術論文
C2 - 16979015
AN - SCOPUS:33748437572
SN - 0735-1097
VL - 48
SP - 1257
EP - 1264
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 6
ER -