Abstract
Background: Mitochondrial dysfunction such as impaired mitophagy and metabolic re-programming has been reported in chronic obstructive pulmonary disease (COPD). Mitochondrial transfer between stem cells and damaged airway smooth muscle cells (ASMC) can reverse the inflammatory consequences of mitochondrial dysfunction (Li et al JACI 2017).
Aim: To understand the process of mitochondrial transfer between ASMCs from healthy ex-smokers and COPD patients
Methods: Mitochondria donor cells were stained with the mitochondrial dye MitoTracker and recipient cells with CellTrace cytoplasmic dye. Cells were directly co-cultured and exposed to transforming growth factor-β (TGF-β 1-10 ng/ml) or cigarette smoke medium (CSM (10-25 %)). Mitochondrial transfer was quantified by flow cytometry and visualised by fluorescence microscopy.
Results: Mitochondrial transfer occurred between ASMCs from ex-smoker and COPD subjects. At baseline, 41.6% (median; range: 12-80%) of cells received mitochondria. There was no difference in the ability of ex-smoker or COPD cells to donate or receive mitochondria. Mitochondrial transfer was inhibited by TGF-β (~20%; p<0.01) and increased by CSM (~2-fold; p<0.01). Mitochondria were transferred via tunnelling nanotubes, and also likely via extracellular vesicles.
Conclusions: Transfer of mitochondria occurs between ASMCs, a process regulated by inflammation and cellular stress. Modulating mitochondrial transfer could be an effective strategy for the treatment of COPD.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, OA3590.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019