Neutrophilic involvement in the damage to coronary arteries in acute stage of Kawasaki disease

Takahashi, Kei; Oharaseki, Toshiaki; Naoe, Shiro; Wakayama, Megumi; Yokouchi, Yuki

doi:10.1111/j.1442-200x.2005.02049.x

Cited by 156 publications

(114 citation statements)

References 13 publications

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“…Histologically, edematous changes are seen in the media in the early phase of KD, which progress to neutrophil and macrophage infiltration in the intima and adventitia. 2 These changes in the coronary artery wall decrease wall tension, resulting in dilatation. After the convalescence phase, the internal and external elastic lamina and smooth muscle cells in the media are damaged by severe inflammation.…”

Section: Resultsmentioning

confidence: 99%

On What Day of Illness Does the Dilatation of Coronary Arteries in Patients With Kawasaki Disease Begin?

Fuse

Mori

Kuroiwa

et al. 2018

Circ J

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Section: Resultsmentioning

confidence: 99%

On What Day of Illness Does the Dilatation of Coronary Arteries in Patients With Kawasaki Disease Begin?

Fuse

Mori

Kuroiwa

et al. 2018

Circ J

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“…Takahashi et al demonstrated the infiltration of numerous neutrophils (anti-elastase-positive neutrophils) in CALs during the early phase of KD (seventh to ninth day of illness), before the infiltration of macrophages and lymphocytes, suggesting that neutrophils are involved in the initial damage that occurs to the coronary arteries [18].…”

Section: The Increased Number Of Neutrophils and The Morphological Chmentioning

confidence: 99%

The Role of Neutrophil Activation in the Pathogenesis of Kawasaki Disease

Takeshita¹,

Kawamura²,

Kanai³

et al. 2018

Pediatric Infect Dis

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In the acute phase of Kawasaki disease (KD), there is an increase in the number of circulating neutrophils, including toxic neutrophils, which are caused by a morphological change. The functions of the neutrophils are also activated, leading to the excessive production of reactive oxygen species and elastase, which may induce endothelial cell (EC) injury. Histological findings demonstrate that numerous neutrophils infiltrate into coronary artery lesions (CALs) during the early phase of KD. Thus, it is suggested that neutrophil-mediated EC injury may be involved in the formation of CALs in KD patients. In this review, we focus on the role of neutrophil activation in the pathogenesis of KD vasculitis and discuss the methods of treatment for neutrophil-mediated EC injury.

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“…42 Considering the role of CXCL12 in the recruitment, adhesion and migration of inflammatory cells, we from KD patients, especially IVIG-resistant patients. Like in the aforementioned studies, our data suggest that IL-6 may be associated with IVIG responsiveness in KD patients.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Analysis of Intravenous Immunoglobulin Resistance in Kawasaki Disease Using an Induced Pluripotent Stem Cell Disease Model

Ikeda

Mizoro

Ameku

et al. 2017

Circ J

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vation of the immune system, with elevations in serum pro-inflammatory cytokines and chemokines, such as interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α. 3-5 The major source of these cytokines and chemokines has remained a mystery. A previous report analyzed the activation status of peripheral blood mononuclear cells (PBMNCs) by flow cytometry, DNA microarray and quantitative reverse transcription polymerase chain reaction (RT-PCR), finding evidence that the innate immune system appeared to play a role in the pathogenesis and pathophysiology of KD, but it also found that PBMNCs had a low expression of pro-inflammatory cytokine genes. 6 It has therefore been K awasaki disease (KD) is an acute febrile disorder characterized by systemic vasculitis and a high predilection for infants and young children. Although ~5 decades have passed since the disease was first described, 1 its etiology still remains unknown. Approximately 25% of untreated KD patients suffer from coronary artery abnormalities, but the frequency of coronary artery sequelae decreases to 2.8% if treatment with high-dose intravenous immunoglobulin (IVIG) is used. 2 However, ~10-20% of KD patients have persistent fever after this treatment and a high risk for coronary artery sequelae.KD in the acute phase is characterized by marked acti- Background: Approximately 10-20% of Kawasaki disease (KD) patients are resistant to intravenous immunoglobulin (IVIG) treatment. Further, these patients are at a particularly high risk of having coronary artery abnormalities. The mechanisms of IVIG resistance in KD have been analyzed using patient leukocytes, but not patient vascular endothelial cells (ECs). The present study clarifies the mechanisms of IVIG resistance in KD using an induced pluripotent stem cell (iPSC) disease model. Methods and Results:Dermal fibroblasts or peripheral blood mononuclear cells from 2 IVIG-resistant and 2 IVIG-responsive KD patients were reprogrammed by the episomal vector-mediated transduction of 6 reprogramming factors. KD patient-derived iPSCs were differentiated into ECs (iPSC-ECs). The gene expression profiles of iPSC-ECs generated from IVIG-resistant and IVIG-responsive KD patients were compared by RNA-sequencing analyses. We found that the expression of CXCL12 was significantly upregulated in iPSC-ECs from IVIG-resistant KD patients. Additionally, Gene Set Enrichment Analysis (GSEA) revealed that gene sets involved in interleukin (IL)-6 signaling were also upregulated. Conclusions:The first iPSC-based model for KD is reported here. Our mechanistic analyses suggest that CXCL12, which plays a role in leukocyte transmigration, is a key molecule candidate for IVIG resistance and KD severity. They also indicate that an upregulation of IL-6-related genes may be involved in this pathogenesis.

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Neutrophilic involvement in the damage to coronary arteries in acute stage of Kawasaki disease

Abstract: These results suggest that neutrophils are involved in the damage occurring to coronary arteries in the early stage of KD. Vasodilation might occur as a result of injury to vascular walls caused by neutrophils, as well as macrophages.

Cited by 156 publications

References 13 publications

On What Day of Illness Does the Dilatation of Coronary Arteries in Patients With Kawasaki Disease Begin?

On What Day of Illness Does the Dilatation of Coronary Arteries in Patients With Kawasaki Disease Begin?

The Role of Neutrophil Activation in the Pathogenesis of Kawasaki Disease

Transcriptional Analysis of Intravenous Immunoglobulin Resistance in Kawasaki Disease Using an Induced Pluripotent Stem Cell Disease Model

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