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.
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.
Authors: Andrei Maiseyeu; Marcus A Badgeley; Thomas Kampfrath; Georgeta Mihai; Jeffrey A Deiuliis; Cuiqing Liu; Qinghua Sun; Sampath Parthasarathy; Daniel I Simon; Kevin Croce; Sanjay Rajagopalan Journal: Arterioscler Thromb Vasc Biol Date: 2012-02-02 Impact factor: 8.311
Authors: Wen Fury; Adriana H Tremoulet; Virginia E Watson; Brookie M Best; Chisato Shimizu; Jennifer Hamilton; John T Kanegaye; Yi Wei; Chiayi Kao; Scott Mellis; Calvin Lin; Jane C Burns Journal: Hum Immunol Date: 2010-06-20 Impact factor: 2.850
Authors: Kevin Croce; Huiyun Gao; Yunmei Wang; Toshifumi Mooroka; Masashi Sakuma; Can Shi; Galina K Sukhova; René R S Packard; Nancy Hogg; Peter Libby; Daniel I Simon Journal: Circulation Date: 2009-07-20 Impact factor: 29.690
Authors: Ruth J Pepper; Juliana B Draibe; Ben Caplin; Fernando C Fervenza; Gary S Hoffman; Cees G M Kallenberg; Carol A Langford; Paul A Monach; Philip Seo; Robert Spiera; E William St Clair; Nadia K Tchao; John H Stone; Ulrich Specks; Peter A Merkel; Alan D Salama Journal: Arthritis Rheumatol Date: 2017-01 Impact factor: 10.995
Authors: Ruth J Pepper; Sally Hamour; Konstantia-Maria Chavele; Sarah K Todd; Niels Rasmussen; Shaun Flint; Paul A Lyons; Kenneth G C Smith; Charles D Pusey; H Terence Cook; Alan D Salama Journal: Kidney Int Date: 2013-02-20 Impact factor: 10.612