Neutrophil extracellular traps (NETs) in COPD: A potential novel mechanism for host damage in acute exacerbations

Abstract

Neutrophilic inflammation is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Neutrophil extracellular traps (NETs) are bacteriocidal but may cause significant host damage. NETs have been implicated in the pathology of inflammatory lung disease 1 but their role in COPD is unknown. We aimed to determine if NET formation was altered in COPD both when stable and during an acute exacerbation (AE-COPD) compared to healthy controls (HC). NET production was measured in peripheral blood neutrophils isolated from age-matched patients with AE-COPD (n=8), stable COPD (n=10) and HC (n=10) in response to inflammatory stimuli. AE-COPD NET formation was quantified upon hospital admission (Day 1) and Days 7 and 14. Cell-free DNA (cfDNA) was quantified in plasma from AE-COPD (n=20 at day 1, 7 and 14); stable COPD (n=20); and HC (n=20). AE-COPD NET formation was reduced in the basal state (p=0.02) and IL8 (p=0.03) compared to stable patients and was reduced to IL8 (p=0.02) compared to HC. This reduction resolved by 14 days post-admission (IL8: p=0.04). cfDNA was increased during the initial phase of exacerbation vs stable COPD (p= 2 =0.63; p=0.03), but not at subsequent time points (day 7: p=0.85, day 14: p=0.22). During AE-COPD, NET formation is transiently suppressed while cfDNA remains elevated. We propose that lower NET production may inhibit bacterial clearance while high remaining circulatory cfDNA might add to systemic host damage by curtailing inflammatory resolution. 1 Saffarzadeh et al , PLoS one, 2013. 7(2): e32366.