Evidence of eosinophil extracellular trap cell death in COPD: does it represent the trigger that switches on the disease?

LOLI URIBE ECHEVARRÍA; ALBERTO NEVADO; AMADO QUINTAR; JORGE GARCÍA GONZÁLEZ; LUCIANA GARCÍA; CAROLINA LEIMGRUBER; RUTH ÁLVAREZ; CRISTINA A MALDONADO

International journal of chronic obstructive pulmonary disease

Auckland, N.Z. : DOVE Medical Press,

Año: 2017 vol. 12 p. 885 - 896

1176-9106

In spite of the numerous studies on Chronic Obstructive Pulmonary Disease (COPD), the cellular and molecular basis of the disease?s development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil death by NETosis, a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about this cell death type for eosinophils (EETosis) and its role in the pathogenesis of COPD.The aim of this study was to evaluate EETosis in stable COPD. Induced sputum (IS) obtained from healthy smokers (HS) and COPD patients with low (LER) COPD A-B or high exacerbation rates (HER) COPD C-D were included. Samples were examined using electron microscopy and immunofluorescence. HS (n=10) and COPD A (n=19) exhibited neutrophilic or paucigranulocytic phenotypes, with NETosis being absent in these patients. In contrast, COPD B (n=29), with eosinophilic or mixed phenotypes, showed EETosis and incipient NETosis. COPD C (n=18) and COPD D (n=13) were differentiated from LER-COPD by the abundant cellular debris, with COPD C having an eosinophilic pattern and numerous EETotic cells. A hallmark of this group was the abundant released membranes which often appeared phagocytosed by neutrophils that coincidentally exhibited pre-NETotic changes. The COPD D group included patients with a neutrophilic or mixed pattern, with abundant NET-derived material.This study is the first to demonstrate EETosis at different stages of stable COPD. The results suggest a role for eosinophils in COPD pathophysiology, especially at the beginning and during the persistence of the disease, regardless of whether the patient quit smoking, with EETosis debris probably triggering uncontrolled NETosis. The main target of these findings should be young smokers with the potential to develop COPD.