Enhanced iNOS expression in leukocytes and circulating endothelial cells is associated with the progression of coronary artery lesions in acute Kawasaki disease.
Nitric oxide (NO) serves many vasoprotective roles, but the massive release of NO causes arterial wall degeneration. We investigated whether enhanced nitric oxide synthase (iNOS) expression in peripheral blood leukocytes and circulating endothelial cells mirrors the progression of coronary arterial lesions in 55 children with acute Kawasaki disease (KD), including 24 with and 31 without coronary artery lesions (CAL). Patients were treated with i.v. gamma-globulin at the time of diagnosis and blood samples were collected before and after treatment. The cellular origin of NO synthesis was determined by flow cytometric analysis of iNOS expression in peripheral blood, and by immunohistochemical analysis of circulating endothelial cells and coronary arteries. iNOS expression in neutrophils peaked at the time of diagnosis, but did not peak in monocytes until 2 wk post onset of disease. Levels were significantly higher in both cell types in patients with CAL (p = 0.001 and p = 0.035, respectively). In addition, the number of circulating endothelial cells and levels of iNOS expression were higher in patients with CAL (p = 0.011 and p = 0.012, respectively). Immunohistochemical analysis of the coronary arteries from three patients with acute KD revealed iNOS immunoreactivity in endothelial cells, as well as infiltrating monocytes/macrophages in the aneurysms. We conclude that the expression of iNOS in peripheral blood leukocytes, as well as circulating endothelial cells, correlates with the severity of coronary arterial wall injury and the progression of CAL in patients with acute KD.
Yu
Xianyi
X
Department of Pediatrics, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama, 930-0194 Japan.
Hirono
Kei-Ich
KI
Ichida
Fukiko
F
Uese
Kei-Ichiro
K
Rui
Chen
C
Watanabe
Sayaka
S
Watanabe
Kazuhiro
K
Hashimoto
Ikuo
I
Kumada
Tokimasa
T
Okada
Eikichi
E
Terai
Masaru
M
Suzuki
Atsuko
A
Miyawaki
Toshio
T
D001158:Arteries / Q000033:anatomy & histology / Q000201:enzymology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003326:Coronary Circulation; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007962:Leukocytes / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology; D008297:Male; D009000:Monocytes / Q000201:enzymology; D009080:Mucocutaneous Lymph Node Syndrome / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II
D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II