Neutrophil extracellular traps induced by a monoclonal anti-phosphatidylserine/prothrombin antibody activate platelets in vitro

Arai, Suishin; Takai, Koki; Miyatake, Hiyori et al.

Experimental and Molecular Pathology, 2026, 147

Permalink : https://hdl.handle.net/2115/100213

このアイテムのアクセス数:27件（2026-09-06 09:37 集計）

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アクセス権
open access
URI
https://hdl.handle.net/2115/100213
タイトル
Neutrophil extracellular traps induced by a monoclonal anti-phosphatidylserine/prothrombin antibody activate platelets in vitro
著者
Arai, Suishin ; Takai, Koki ; Miyatake, Hiyori ; Oshima, Yuka ; Manabe, Riku ; Nishibata, Yuka ; Abe, Takumi ; Sasaki, Ayana ; Fukuyama, Mizuki ; Washio, China ; Ogawa, Naho ; Ogawa, Hodaka ; Hori, Ikuma ; Watanabe-Kusunoki, Kanako ; Nakazawa, Daigo ; Masuda, Sakiko ; Tomaru, Utano ; Ishizu, Akihiro
著者名
Arai, Suishin
著者名
Takai, Koki
著者名
Miyatake, Hiyori
著者名
Oshima, Yuka
著者名
Manabe, Riku
ORCID
0009-0002-6971-0652
著者名
Nishibata, Yuka
ORCID
0000-0003-1729-1097
著者名
Abe, Takumi
著者名
Sasaki, Ayana
著者名
Fukuyama, Mizuki
著者名
Washio, China
著者名
Ogawa, Naho
著者名
Ogawa, Hodaka
ORCID
0009-0000-3260-5440
著者名
Hori, Ikuma
ORCID
0000-0001-8760-8630
著者名
Watanabe-Kusunoki, Kanako
著者名
Nakazawa, Daigo
ORCID
0009-0006-8414-7094
著者名
Masuda, Sakiko
ORCID
0000-0001-7929-9874
著者名
Tomaru, Utano
ORCID
0000-0002-7084-9734
著者名
Ishizu, Akihiro
言語
英語
キーワード
Antiphospholipid syndrome
Anti-phosphatidylserine/prothrombin antibodies
Monoclonal antibodies
Neutrophil extracellular traps
Histone H3
発行日
2026-09
出版者
Elsevier
収録物名
Experimental and Molecular Pathology
巻(号)
147
抄録
Antiphospholipid syndrome (APS) is an autoimmune thrombotic disorder characterized by the presence of antiphospholipid antibodies, including anti-phosphatidylserine/prothrombin antibodies (aPS/PT). While neutrophil extracellular traps (NETs) are implicated in the pathogenesis of APS, the role of aPS/PT in NET induction and its contribution to thrombosis remain unclear. This study aimed to clarify the effects of NETs induced by a monoclonal aPS/PT antibody on platelet activation and their potential contribution to thrombo-inflammatory responses. NETs were induced by stimulating peripheral blood neutrophils from healthy donors with aPS/PT. Their morphology and platelet-activating capacity were compared with NETs induced by anti-neutrophil cytoplasmic antibodies (ANCAs). Proteomic analyses were conducted to comprehensively compare protein compositions of these NETs, and candidate proteins associated with platelet activation in aPS/PT-induced NETs were identified. Functional inhibition assays were then conducted to assess whether blocking these candidates would suppress aPS/PT-induced NET-mediated platelet activation. We found that binding of aPS/PT to neutrophils induced NET formation, with a larger and more fibrous morphology compared to ANCA-induced NETs. Platelets trapped in aPS/PT-induced NETs showed significantly higher activation compared to those trapped in ANCA-induced NETs. Proteomic analyses identified histone H3 as a potential mediator of platelet activation in aPS/PT-induced NETs. Correspondingly, plasma concentrations of H3.1 nucleosome were significantly higher in patients with APS than in healthy controls. Blockade of histone H3 using a neutralizing antibody significantly suppressed platelet activation mediated by aPS/PT-induced NETs. These findings suggest that aPS/PT-induced NETs contribute to platelet activation and may promote thrombo-inflammatory responses in APS. Targeting histone H3 within aPS/PT-induced NETs may provide a potential therapeutic strategy for thrombo-inflammatory processes in APS.
資源タイプ
学術雑誌論文
出版タイプ
Version of Record
権利情報
Creative Commons Attribution-NonCommercial 4.0 International
PISSN
0014-4800
関連情報
PMID
42531670
関連情報 (isIdenticalTo)
出版社版DOI
https://doi.org/10.1016/j.yexmp.2026.105070