Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2954902 | Journal of the American College of Cardiology | 2006 | 8 Pages |
ObjectivesThis 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.BackgroundBoth 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.MethodsWe 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.ResultsThe 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.ConclusionsWe 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.