Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease.
OBJECTIVE
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.
Hirono
Keiich
K
Department of Pediatrics, Toyama University, Toyama, Japan.
Foell
Dirk
D
Xing
Yanlin
Y
Miyagawa-Tomita
Sachiko
S
Ye
Fei
F
Ahlmann
Martina
M
Vogl
Thomas
T
Futatani
Takeshi
T
Rui
Chen
C
Yu
Xianyi
X
Watanabe
Kazuhiro
K
Wanatabe
Sayaka
S
Tsubata
Shinichi
S
Uese
Keiichiro
K
Hashimoto
Ikuo
I
Ichida
Fukiko
F
Nakazawa
Makoto
M
Roth
Johannes
J
Miyawaki
Toshio
T
D000208:Acute Disease; D001773:Blood Cells / Q000473:pathology; D040501:Calgranulin A / Q000097:blood* / Q000235:genetics; D040502:Calgranulin B / Q000097:blood* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D040501:Calgranulin A; D040502:Calgranulin B; D016756:Immunoglobulins, Intravenous; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha