Abstract
[Objectives] Circulating polymorphonuclear neutrophils(PMNs) are known to increase in number and are functionally activated in the acute phase of Kawasaki disease(KD). The aim of the present study is to investigate whether the apoptosis of PMNs is deregulated in acute KD. [Patients and methods] We studied the apoptosis of PMNs (AnnexinV-positive cells and cells with fragmented DNA) and the expression of Fas(CD95) and Bcl-2 protein(A1, Bax) using flow cytometer in KD patients(n=25), patients with a bacterial infection(BI, n=20), viral infection(VI, n=20) and healthy children(HC, n=20). [Results] When the isolated PMNs were cultured in vitro, the proportions of spontaneous apoptotic PMNs were found to be significantly lower (P<0.01) in the acute KD patients than in BI, VI or HC. The proportion of circulating Fas(CD95)-positive PMNs was also significantly lower (P<0.01) in the acute KD patients than in the other groups. In the acute phase of KD, the proportion of spontaneous apoptotic PMNs showed both a significant negative-correlation (P<0.01) with the peripheral PMN counts and a significant positive-correlation (P<0.01) with the proportions of circulating Fas(CD95)-positive PMNs. Furthermore, the agonistic anti-Fas mAb(CH-11) induced a significant increase in the proportion of apoptotic PMNs in the patients with a viral infection and healthy children, but not in either the patients with acute KD or the patients with a bacterial infection. In the intracellular expression of anti-(A1) and pro-apoptotic protein(Bax), the A1/Bax ratio was significantly higher in acute KD than in the other groups. [Conclusions] These findings indicate that PMN apoptosis is inhibited during the acute phase of KD and also suggest that both the resistance against the Fas-mediated death signal and the down-regulation of the mitochondrial apoptotic signaling pathway due to an altered balance of Bcl-2 protein expression are responsible for the delayed PMN apoptosis.
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Tsujimoto, H., Takeshita, S., Nakatani, K. et al. Neutrophil Apoptosis is Inhibited in the Acute Phase of Kawasaki Disease. Pediatr Res 53, 170 (2003). https://doi.org/10.1203/00006450-200301000-00102
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DOI: https://doi.org/10.1203/00006450-200301000-00102