Hypoxia linked to Neutrophil-mediated endothelial damage in COPD, study reveals

UK: Insights from a recent study in the American Journal of Respiratory and Critical Care Medicine may help to identify new therapeutic opportunities for endothelial damage in chronic obstructive pulmonary disease (COPD).

According to the study, hypoxia drives a destructive "hypersecretory" neutrophil phenotype resulting in enhanced capacity for endothelial damage, with a corresponding signature of vascular injury and neutrophil degranulation identified in the plasma of COPD patients. This implies that hypoxic enhancement of neutrophil degranulation may lead to increased cardiovascular risk in COPD. 

COPD patients are reported to be at increased risk of excess cardiovascular morbidity and mortality, and exacerbation worsens the risk. COPD is associated with persistent blood and airway neutrophilia and systemic and tissue hypoxia. Hypoxia augments the release of neutrophil elastase enhancing the capacity for tissue injury. Thus, hypoxic neutrophils have increased potential to cause endothelial injury, but their role in mediating the increased cardiovascular risk in COPD is poorly understood.

To fill the knowledge gap described above, Katharine M. Lodge, National Heart and Lung Institute, Imperial College London, London, United Kingdom, and colleagues aimed to determine whether hypoxia-driven neutrophil protein secretion contributes to endothelial damage in COPD.

For this purpose, the researchers used quantitative mass spectrometry for characterizing the healthy human neutrophil secretome generated under normoxic or hypoxic conditions and an assessment of the capacity for neutrophil-mediated endothelial damage was done. 

Histotoxic protein concentrations were measured in normoxic versus hypoxic neutrophil supernatants and plasma from patients experiencing COPD exacerbation and healthy control subjects. 

"We provide the first description of hypoxia's ability to augment the secretion of histotoxic proteins from COPD neutrophils in vitro and have identified a corresponding increase in the plasma concentrations of selected granule proteins and markers of vascular injury in patients with COPD," the authors wrote in their study

"Our findings may illuminate novel therapeutic targets in treatment-recalcitrant neutrophil-mediated inflammatory diseases such as COPD," they concluded.

Reference:

Lodge, K.M., Vassallo, A., Liu, B. et al. (15 more authors) (2022) Hypoxia increases the potential for neutrophil-mediated endothelial damage in COPD. American Journal of Respiratory and Critical Care Medicine. ISSN 1073-449X. https://doi.org/10.1164/rccm.202006-2467oc