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<p>Wood smoke (WS)-derived PM<sub>2.5</sub> is a major environmental risk factor for emphysema, but the role of macrophage-derived exosomes remains unclear. Here, we show that chronic WS exposure in rats induces emphysematous lesions accompanied by markedly increased exosome release, reflected by elevated CD63 expression in alveoli and increased exosome particle number in bronchoalveolar lavage fluid. Pharmacological inhibition of exosome secretion with GW4869 significantly attenuated alveolar destruction. Moreover, intranasal administration of exosomes from PM<sub>2.5</sub>-exposed macrophages was sufficient to recapitulate emphysematous pathology <i>in vivo</i>. Mechanistically, PM<sub>2.5</sub> exposure upregulated the membrane-trafficking protein SNAP23 in macrophages, enhancing exosome secretion and increasing total abundance of ADAM10 within exosomes. Co-localization of CD63 and ADAM10 was observed in alveolar regions of WS-exposed rats and COPD patient lungs. Silencing ADAM10 suppressed caspase-3 activation and reduced epithelial apoptosis, supporting a role for exosomal ADAM10 in driving caspase-3–dependent alveolar epithelial injury. By defining an exosome-mediated macrophage–epithelium pathway that contributes to PM<sub>2.5</sub>-induced emphysema, this study clarifies how combustion-derived PM<sub>2.5</sub> damages lung structure and offers mechanistic insight to reducing the health burden of biomass-related air pollution.</p> Graphical Abstract <p>1. Chronic wood smoke exposure increases exosome release in rat lungs.</p> <p>2. PM<sub>2.5</sub> upregulates SNAP23 in macrophages, promoting exosome secretion and ADAM10 enrichment.</p> <p>3. Macrophage exosomal ADAM10 induces alveolar epithelial apoptosis via caspase-3 activation.</p> <p>4. Targeting exosome release or ADAM10 offer potential strategies for PM<sub>2.5</sub>-induced emphysema.</p> <p></p>

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Macrophage exosomal ADAM10 mediates alveolar epithelial apoptosis induced by wood smoke PM2.5

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月29日

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  • Na Zhan,
  • Yufeng Wang,
  • Ru Liang,
  • Yousen Wu,
  • Ting Huang,
  • Yuquan Ling,
  • Xinbei Chen,
  • Jiacheng Deng,
  • LiFen Zhou,
  • Kangni Luo,
  • Yilin Cai,
  • Yong-sheng Tu,
  • Lihui Qu,
  • Jianhua Li

摘要

Wood smoke (WS)-derived PM2.5 is a major environmental risk factor for emphysema, but the role of macrophage-derived exosomes remains unclear. Here, we show that chronic WS exposure in rats induces emphysematous lesions accompanied by markedly increased exosome release, reflected by elevated CD63 expression in alveoli and increased exosome particle number in bronchoalveolar lavage fluid. Pharmacological inhibition of exosome secretion with GW4869 significantly attenuated alveolar destruction. Moreover, intranasal administration of exosomes from PM2.5-exposed macrophages was sufficient to recapitulate emphysematous pathology in vivo. Mechanistically, PM2.5 exposure upregulated the membrane-trafficking protein SNAP23 in macrophages, enhancing exosome secretion and increasing total abundance of ADAM10 within exosomes. Co-localization of CD63 and ADAM10 was observed in alveolar regions of WS-exposed rats and COPD patient lungs. Silencing ADAM10 suppressed caspase-3 activation and reduced epithelial apoptosis, supporting a role for exosomal ADAM10 in driving caspase-3–dependent alveolar epithelial injury. By defining an exosome-mediated macrophage–epithelium pathway that contributes to PM2.5-induced emphysema, this study clarifies how combustion-derived PM2.5 damages lung structure and offers mechanistic insight to reducing the health burden of biomass-related air pollution.

Graphical Abstract

1. Chronic wood smoke exposure increases exosome release in rat lungs.

2. PM2.5 upregulates SNAP23 in macrophages, promoting exosome secretion and ADAM10 enrichment.

3. Macrophage exosomal ADAM10 induces alveolar epithelial apoptosis via caspase-3 activation.

4. Targeting exosome release or ADAM10 offer potential strategies for PM2.5-induced emphysema.