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<p><i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>)-associated bronchiectasis remains a clinical challenge due to lacking diagnostic biomarkers and targeted therapies. This multi-dimensional (clinical-cell-animal) study investigated the myeloperoxidase (MPO)-DNA complex, a marker of neutrophil extracellular traps (NETs), and the combination of AZD5904 (an MPO inhibitor) and DNase I (a NETs-DNA degrader). Key findings include: First, integrated evidence from bronchoalveolar lavage fluid analysis and immunofluorescence identified the MPO-DNA complex as a biomarker significantly associated with <i>P. aeruginosa</i>-associated bronchiectasis severity (e.g., lung lobe involvement, Bronchiectasis Severity Index). Mendelian randomization (MR) analysis revealed a potential causal link with bronchiectasis risk but not with several other chronic respiratory diseases. Second, in cellular models, <i>P. aeruginosa</i> PAO1-induced NETs were associated with epithelial damage, as evidenced by the upregulation of reactive oxygen species, malondialdehyde, interleukin-1β, and interleukin-6, and the reduction of BEAS-2B cell viability. Third, in <i>P. aeruginosa</i>-infected bronchiectasis rat models, AZD5904 combined with DNase I alleviated lung pathology, inflammation, and NETs accumulation more effectively than monotherapy. This study suggests the MPO-DNA complex as a potential biomarker and pathogenic factor associated with disease severity, and proposes a dual-target combined intervention strategy worthy of further preclinical investigation for <i>P. aeruginosa</i>-associated bronchiectasis.</p>

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Myeloperoxidase-DNA complex: a marker and combined target for Pseudomonas aeruginosa-associated bronchiectasis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月22日

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  • Shaochu Zheng,
  • Jinling Tang,
  • Xiaopu Wu,
  • Cao Qing,
  • Yun Jiang,
  • Wei Lu,
  • Chongxi Bao,
  • Kangkang Hong,
  • Jing Luo,
  • Jinliang Kong

摘要

Pseudomonas aeruginosa (P. aeruginosa)-associated bronchiectasis remains a clinical challenge due to lacking diagnostic biomarkers and targeted therapies. This multi-dimensional (clinical-cell-animal) study investigated the myeloperoxidase (MPO)-DNA complex, a marker of neutrophil extracellular traps (NETs), and the combination of AZD5904 (an MPO inhibitor) and DNase I (a NETs-DNA degrader). Key findings include: First, integrated evidence from bronchoalveolar lavage fluid analysis and immunofluorescence identified the MPO-DNA complex as a biomarker significantly associated with P. aeruginosa-associated bronchiectasis severity (e.g., lung lobe involvement, Bronchiectasis Severity Index). Mendelian randomization (MR) analysis revealed a potential causal link with bronchiectasis risk but not with several other chronic respiratory diseases. Second, in cellular models, P. aeruginosa PAO1-induced NETs were associated with epithelial damage, as evidenced by the upregulation of reactive oxygen species, malondialdehyde, interleukin-1β, and interleukin-6, and the reduction of BEAS-2B cell viability. Third, in P. aeruginosa-infected bronchiectasis rat models, AZD5904 combined with DNase I alleviated lung pathology, inflammation, and NETs accumulation more effectively than monotherapy. This study suggests the MPO-DNA complex as a potential biomarker and pathogenic factor associated with disease severity, and proposes a dual-target combined intervention strategy worthy of further preclinical investigation for P. aeruginosa-associated bronchiectasis.