MPO

MPO (Myeloperoxidase)

一行要約

好中球の azurophilic granule (一次顆粒) に高濃度で蓄積される heme-containing peroxidase で、H2O2 と Cl⁻ から強力な酸化剤 hypochlorous acid (HOCl) を生成して殺菌・組織損傷・Neutrophil-extracellular-traps (NET) 構成因子として機能する。NET 上の MPO-DNA complex は血清 / 組織で測定可能な NET formation の代表的 surrogate marker であり、cancer-associated thrombosis、ARDS、心血管疾患、神経変性疾患でバイオマーカーとして利用される。

主要エビデンス

NET 構成・処理因子: MPO は PAD4 (PAD4)・neutrophil elastase (NE) と協調して核内 chromatin の processing を駆動し、citH3 陽性 decondensed chromatin の細胞外放出を支える。Metzler ら (Cell Rep 2014) は MPO 欠損好中球で NET 形成能が部分的に低下することを示した。

血清 NET marker としての臨床応用: Thålin ら (Arterioscler Thromb Vasc Biol 2017 ほか) で MPO-DNA complex / citH3-DNA complex が ELISA で定量可能な NET surrogate として確立され、cancer-associated thrombosis、severe COVID-19、ARDS、敗血症で全身的 NET 活性の biomarker として使用される。Mauracher ら (J Thromb Haemost 2018) は VTE を発症した cancer 患者で baseline circulating citH3 / MPO-DNA が上昇していることを示した。

腫瘍微小環境での機能: 腫瘍浸潤好中球 (TAN) の MPO 高活性は HOCl 産生を介して DNA 損傷・腫瘍細胞 senescence・血管透過性亢進・転移促進に寄与する一方、抗腫瘍 cytotoxicity の側面も持つ文脈依存的因子。

メカニズム

酵素反応: H2O2 + Cl⁻ + H⁺ → HOCl + H2O。HOCl は強力な微生物殺菌作用を持つ一方、host tissue protein の chlorination・lipid peroxidation・DNA 損傷を引き起こし、過剰活性は組織損傷 / 慢性炎症に直結する。

Granule biology: 好中球分化過程の promyelocyte 期に主として合成され、azurophilic granule (一次顆粒) に蓄積される。脱顆粒 / NETosis 時に細胞外に放出され、NET 上 chromatin に共結合した状態で MPO-DNA 複合体として検出される。NET 由来 MPO は通常の granule 由来 MPO と区別困難なため、MPO-DNA ELISA では DNA 共局在を捕捉条件にして specificity を確保している。

薬理学的標的化: AZD4831 (verdiperstat) は経口 MPO 阻害剤として ANCA 関連血管炎・Multiple System Atrophy で臨床試験中。がん領域での開発は前臨床段階。

関連エンティティ・概念

• NET formation co-factor: PAD4 / NE (neutrophil elastase) / HIF1A
• Concept: Neutrophil-extracellular-traps / NETosis-cancer-metastasis / Cancer-associated-thrombosis
• MOC: cancer-neutrophils

関連論文

直近 30 件のみ表示中 (関連 139 件)。 全件は MOC ページ または Obsidian (source Markdown) から辿れます。

Basic-Brain metastasis

• Cai et al. FrontImmunol 2026 — Mechanistic and functional characterization of NETsIL-17 as a therapeutic target in EMT and brain metastasis of lung

Basic-Extracellular vesicles

• Zhang et al. CellRepMed 2026 — Artificial exosomes synergistically reshape sepsis immune homeostasis by modulating neutrophil fate and blocking
• Xie et al. IntImmunopharmacol 2025 — Neutrophil-derived exosomes promote sepsis-related multiple organ dysfunction through the induction of neutrophil
• Richter et al. STARProtoc 2025 — Protocol for the isolation of human neutrophil-derived extracellular vesicles for characterization and functional

Basic-Immunotherapy

• Yue et al. Cell 2026 — Expansion and CAR engineering of granulocyte-monocyte progenitors for cellular immunotherapy

Basic-Neutrophil and myeloid cell

• Zeng et al. ACSNano 2024 — Neutrophil nanodecoys inhibit tumor metastasis by blocking the interaction between tumor cells and neutrophils
• He et al. CancerCell 2024 — Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment
• Chen et al. CancerCell 2025 — DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(l)1 therapy efficacy by degrading
• He et al. CancerCell 2025 — Chemotherapy awakens dormant cancer cells in lung by inducing neutrophil extracellular traps
• Lee et al. CancerCell 2025 — Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells
• Bolli et al. CancerCell 2026 — CCL3 is produced by aged neutrophils across cancers and promotes tumor growth
• Sturgeon et al. Cancers 2025 — Neutrophil dynamics contribute to disease progression and poor survival in pancreatic cancer
• Hsu et al. Cell 2025 — Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution
• Qian et al. Cell 2026 — Respiratory viral infections prime accelerated lung cancer growth
• Meng et al. CellRep 2026 — Nociceptive neurons inhibit neutrophil extracellular trap formation via MLKL-licensed histone release
• McDonald et al. CommunBiol 2025 — Neutrophil extracellular trap gene expression signatures identify prognostic and targetable signaling axes for
• Yang et al. FrontImmunol 2025 — Unveiling cd177 a key player in tumors, autoimmune diseases, and inflammatory disorders
• McGarrity-Cottrell et al. FrontImmunol 2026 — Physiological, patho-physiological, and potential therapeutic roles for neutrophils in cancer & beyond
• Wu et al. FrontImmunol 2026 — Tumor-associated neutrophils in pancreatic ductal adenocarcinoma mechanisms and therapeutic targeting
• Baron et al. FrontOncol 2025 — Neutrophil extracellular traps are associated with poor response to neoadjuvant therapy and poor survival in pediatric
• Pires et al. Immunity 2026 — Innate lymphoid cells activated by the cytokine TL1A link colitis to emergency granulopoiesis and the recruitment of
• Wang et al. NatCancer 2026 — CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8
• Sanchez-Garcia et al. NatImmunol 2025 — Hypoxia induces histone clipping and H3K4me3 loss in neutrophil progenitors resulting in long-term impairment of
• Shahzad et al. NatRevCancer 2026 — Neutrophil extracellular traps in cancer
• Adrover et al. Nature 2025 — Neutrophils drive vascular occlusion, tumour necrosis and metastasis
• Burn et al. Nature 2025 — Myeloperoxidase transforms chromatin into neutrophil extracellular traps
• Liu et al. Neuron 2025 — Lcn2 from neutrophil extracellular traps induces astrogliosis and post-stroke emotional disorders
• Tavares et al. SciImmunol 2025 — SiglecF neutrophils
• Xu et al. bioRxiv 2026 — Neutrophils repurpose the nucleolus as a cytokine reservoir and secretory organelle

Basic-Others

• Leunig et al. NatRevImmunol 2025 — Connection and communication between the nervous and immune systems