Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis

Abstract Neutrophils form neutrophil extracellular traps (NETs), which are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Recent reports suggest that platelets stimulated via toll-like receptor (TLR) pathways can induce NETs formation. However, the mechanism underlying the involve...

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Autores principales:	Kotaro Matsumoto, Hidekata Yasuoka, Keiko Yoshimoto, Katsuya Suzuki, Tsutomu Takeuchi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f64033369c8343fbb1ed13579f2a4229
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spelling	oai:doaj.org-article:f64033369c8343fbb1ed13579f2a42292021-12-02T15:14:14ZPlatelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis10.1038/s41598-020-80685-42045-2322https://doaj.org/article/f64033369c8343fbb1ed13579f2a42292021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80685-4https://doaj.org/toc/2045-2322Abstract Neutrophils form neutrophil extracellular traps (NETs), which are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Recent reports suggest that platelets stimulated via toll-like receptor (TLR) pathways can induce NETs formation. However, the mechanism underlying the involvement of platelets in NETs formation in AAV is unknown. We investigated the role of platelets in the pathogenesis of AAV. Platelets from AAV patients and healthy controls (HCs) were co-cultured with peripheral neutrophils, and NETs formation was visualized and quantified. The expression levels of TLRs on platelets were examined by flow cytometry. Platelets were treated with a TLR agonist, platelet-derived humoral factor, CXCL4 (platelet factor 4: PF4), and/or anti-CXCL4 antibody to investigate the effects of TLR–CXCL4 signaling on NETs formation. Platelets from AAV significantly upregulated NETs formation in vitro. Flow cytometric analysis revealed that the proportion of TLR9 positive platelets was significantly higher in AAV than HCs. CXCL4 released from TLR9 agonist-stimulated platelets was significantly enhanced in AAV, which subsequently increased NETs formation. Further, neutralizing anti-CXCL4 antibody significantly inhibited NETs formation enhanced by platelets from AAV. TLR9 signaling and CXCL4 release underlie the key role that platelets play in NETs formation in the pathogenesis of AAV.Kotaro MatsumotoHidekata YasuokaKeiko YoshimotoKatsuya SuzukiTsutomu TakeuchiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kotaro Matsumoto Hidekata Yasuoka Keiko Yoshimoto Katsuya Suzuki Tsutomu Takeuchi Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis
description	Abstract Neutrophils form neutrophil extracellular traps (NETs), which are involved in the pathogenesis of ANCA-associated vasculitis (AAV). Recent reports suggest that platelets stimulated via toll-like receptor (TLR) pathways can induce NETs formation. However, the mechanism underlying the involvement of platelets in NETs formation in AAV is unknown. We investigated the role of platelets in the pathogenesis of AAV. Platelets from AAV patients and healthy controls (HCs) were co-cultured with peripheral neutrophils, and NETs formation was visualized and quantified. The expression levels of TLRs on platelets were examined by flow cytometry. Platelets were treated with a TLR agonist, platelet-derived humoral factor, CXCL4 (platelet factor 4: PF4), and/or anti-CXCL4 antibody to investigate the effects of TLR–CXCL4 signaling on NETs formation. Platelets from AAV significantly upregulated NETs formation in vitro. Flow cytometric analysis revealed that the proportion of TLR9 positive platelets was significantly higher in AAV than HCs. CXCL4 released from TLR9 agonist-stimulated platelets was significantly enhanced in AAV, which subsequently increased NETs formation. Further, neutralizing anti-CXCL4 antibody significantly inhibited NETs formation enhanced by platelets from AAV. TLR9 signaling and CXCL4 release underlie the key role that platelets play in NETs formation in the pathogenesis of AAV.
format	article
author	Kotaro Matsumoto Hidekata Yasuoka Keiko Yoshimoto Katsuya Suzuki Tsutomu Takeuchi
author_facet	Kotaro Matsumoto Hidekata Yasuoka Keiko Yoshimoto Katsuya Suzuki Tsutomu Takeuchi
author_sort	Kotaro Matsumoto
title	Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis
title_short	Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis
title_full	Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis
title_fullStr	Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis
title_full_unstemmed	Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis
title_sort	platelet cxcl4 mediates neutrophil extracellular traps formation in anca-associated vasculitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f64033369c8343fbb1ed13579f2a4229
work_keys_str_mv	AT kotaromatsumoto plateletcxcl4mediatesneutrophilextracellulartrapsformationinancaassociatedvasculitis AT hidekatayasuoka plateletcxcl4mediatesneutrophilextracellulartrapsformationinancaassociatedvasculitis AT keikoyoshimoto plateletcxcl4mediatesneutrophilextracellulartrapsformationinancaassociatedvasculitis AT katsuyasuzuki plateletcxcl4mediatesneutrophilextracellulartrapsformationinancaassociatedvasculitis AT tsutomutakeuchi plateletcxcl4mediatesneutrophilextracellulartrapsformationinancaassociatedvasculitis
_version_	1718387607488954368

Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis

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