Concentrations of microplastics, particularly polystyrene microplastics, were significantly higher in the lung tissues of COPD patients compared to controls.
Microplastics may induce mitochondrial dysfunction and iron accumulation, which are associated with autophagy-dependent .
In vitro and in vivo experiments suggest that microplastics can enhance inflammation in COPD.
Exposure to 2 μm polystyrene microplastics leads to their deposition in the lungs of COPD model mice.
Mitochondrial impairments and overproduction of occur alongside increased lysosome biogenesis in response to microplastic exposure.
Alleviating excessive inflammation and acute exacerbation of COPD may be possible through targeting autophagy-dependent ferroptosis.
Simplified
Microplastics (MPs) induce mitochondrial dysfunction and iron accumulation, contributing to mitochondrial macroautophagy/autophagy and , which has increased susceptibility to the exacerbation of chronic obstructive pulmonary disease (COPD); however, the underlying mechanism remains unclear. We demonstrated that MPs intensified inflammation in COPD by enhancing autophagy-dependent ferroptosis (ADF) in vitro and in vivo. In the lung tissues of patients with COPD, the concentrations of MPs, especially polystyrene microplastics (PS-MPs), were significantly higher than that of the control group, as detected by pyrolysis gas chromatography mass spectrometry (Py-GCMS), with increased iron accumulation. The exposure to PS-MPs, 2 μm in size, resulted in their being deposited in the lungs of COPD model mice detected by optical in vivo imaging, and observed in bronchial epithelial cells traced by GFP-labeled PS-MPs. There were mitochondrial impairments accompanied by (mito-ROS) overproduction and significantly increased levels of lysosome biogenesis and acidification in pDHBE cells with PS-MP stimulation, triggering occurrence of ferritinophagy and enhancing ADF in COPD, which triggered acute exacerbation of COPD (AECOPD). Reestablishing autophagy-dependent ferroptosis via mitochondria-specific ROS scavenging or ferroptosis inhibition alleviated excessive inflammation and ameliorated AECOPD induced by PS-MPs. Collectively, our data initially revealed that MPs exacerbate ferroptosis via mito-ROS-mediated autophagy in COPD, which sheds light on further hazard assessments of MPs on human respiratory health and potential therapeutic agents for patients with COPD.ADF: autophagy-dependent ferroptosis; AECOPD: acute exacerbation of chronic obstructive pulmonary disease; Cchord: static compliance; COPD: chronic obstructive pulmonary disease; CQ: chloroquine; CS: cigarette smoke; DEGs: differentially expressed genes; Fer-1: ferrostatin-1; FEV 0.1: forced expiratory volume in first 100 ms; FVC: forced vital capacity; GSH: glutathione; HE: hematoxylin and eosin; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; MDA: malondialdehyde; Mito-ROS: mitochondrial reactive oxygen species; MMA: methyl methacrylate; MMF: maximal mid-expiratory flow curve; MMP: mitochondrial membrane potential; MOI: multiplicity of infection; MPs: microplastics; MV: minute volume; PA: polyamide; PBS: phosphate-buffered saline; PC: polycarbonate; pDHBE: primary human bronchial epithelial cell from COPD patients; PET: polyethylene terephthalate; PIF: peak inspiratory flow; PLA: polylactic acid; pNHBE: primary normal human bronchial epithelial cell; PS-MPs: polystyrene microplastics; PVA: polyvinyl acetate; PVC: polyvinyl chloride; Py-GCMS: pyrolysis gas chromatography mass spectrometry; SEM: scanning electron microscopy; Te: expiratory times; Ti: inspiratory times; TNF/TNF-α: tumor necrosis factor. Abbreviations:
Key numbers
7 of 13 patients
Increased microplastics concentration
Patients with COPD had significantly higher microplastics in lung tissues compared to healthy controls.
200 μg/ml
Cell death threshold
Significant cell death in primary bronchial epithelial cells occurred at this concentration of PS-MPs.
50 μg/ml
Mito-ROS increase
Mito-ROS levels began to rise significantly at this concentration of PS-MPs stimulation.
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