Eosinophils promote pulmonary matrix destruction and emphvsema via Cathepsin L

Patients with chronic obstructive pulmonary disease(COPD)who exhibit elevated blood eosinophil levels often experience worsened lung function and more severe emphysema.This implies the potential involvement of eosinophils in the development of emphysema.However,the precise mechanisms underlying the development of eosinophil-mediated emphysema remain unclear.In this study,we employed single-cell RNA sequencing to identify eosinophil subgroups in mouse models of asthma and emphysema,followed by functional analyses of these subgroups.Assessment of accumulated eosinophils unveiled distinct transcriptomes in the lungs of mice with elastase-induced emphysema and ovalbumin-induced asthma.Depletion of eosinophils through the use of anti-interleukin-5 antibodies ameliorated elastase-induced emphysema.A particularly noteworthy discovery is that eosinophil-derived cathepsin L contributed to the degradation of the extracellular matrix,thereby leading to emphysema in pulmonary tissue Inhibition of cathepsin L resulted in a reduction of elastase-induced emphysema in a mouse model.Importantly,eosinophil levels correlated positively with serum cathepsin L levels,which were higher in emphysema patients than those without emphysema.Expression of cathepsin L in eosinophils demonstrated a direct association with lung emphysema in COPD patients.Collectively,these findings underscore the significant role of eosinophil-derived cathepsin L in extracellular matrix degradation and remodeling,and its relevance to emphysema in coPD patients.Consequently,targeting eosinophil-derived cathepsin L could potentially offer a therapeutic avenue for emphysema patients.Further investigations are warranted to explore therapeutic strategies targeting cathepsin L in emphysema patients.

Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile

Background: Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. Methods: Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results: At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion: COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.