Zhang, Yuan and Jia, Cuiping and Guo, Manli and Chen, Qian and Wen, Ying and Wang, Ting and Xie, Yinyin and Fan, Xuejiao and Gao, Jingwen and Yarovinsky, Timur O. and Liu, Renjing and Jiang, Zhiyong and Wang, Mengmeng and Zhou, Jin and Che, Di and Fu, Lanyan and Edelson, Richard and Gu, Xiaoqiong and Hwa, John and Tang, Wai Ho (2025) Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease. Advanced Science, 12 (5). ISSN 2198-3844
Full text not available from this repository.Abstract
Abstract
Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inflammation and vasculopathy in KD remains unclear. A cytokine‐mediated positive feedback loop between KD platelets and monocytes is identified. KD platelet–monocyte aggregates (MPAs) are mediated by an initial interaction of P‐selectin (cluster of differentiation 62P, CD62p) and its glycoprotein ligand 1 (PSGL‐1). This is followed by a coordinated interaction of platelet glycoprotein (GP)Ibα with monocyte CD11b. Monocyte‐activated platelets initiate transforming growth factor (TGF)β1 release, which results in nuclear localization of nuclear factor kappaB in monocytes, therefore, driving the phenotypic conversion of classical monocytes (CD14 + CD16 − ) into proinflammatory monocytes (CD14 + CD16 + ). The platelet‐activated monocytes release interleukin‐1 and tissue necrotic factor‐α, which promote further platelet activation. KD‐induced inflammation and vasculopathy are prevented by inhibiting the components of this positive feedback loop. Notably, mice deficient in platelet TGFβ1 show less MPA and CD14 + CD16 + monocytes, along with reduced inflammation and vasculopathy. These findings reveal that platelet–monocyte interactive proteins (CD62p/PSGL‐1 and (GP)Ibα/CD11b) and cytokine mediators (platelet TGFβ1) are potential biomarkers and therapeutic targets for KD vasculopathy.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 06:04 |
| Last Modified: | 05 May 2025 06:04 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1676 |
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