229:
Eosinophil autophagy and extracellular DNA traps are involved in severe asthma
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Duy Le Pham, Youngwoo Choi, Ga-Young Ban, Hae-Sim Park, MD PhD FAAAAI
RATIONALE: Activated eosinophils could have high levels of autophagy and produce eosinophil extracellular DNA traps (EETs), which is composed of decondensed nuclear chromatin and eosinophilic granules. Recently, EET was detected in the asthmatic airways; however, the role of autophagy in EET production in asthma has not been studied. We evaluated the levels of autophagy and EET from peripheral blood eosinophils (PBEs) of patients with severe asthma (SA) in comparison to those with non-severe asthma (NSA). The effects of PBE activation on airway epithelial cells (AECs) were also investigated.

METHODS: We compared levels of autophagy and EET production from peripheral blood eosinophils isolated from patients with SA (n=10) and NSA (n=13) by immunocytochemistry. Effects of EETs on airway epithelial cells (AECs) were evaluated in vitro.

RESULTS: Upon IL-5 and LPS stimulation, PBEs from SA patients showed high levels of autophagy (P = 0.022) and EET production (P = 0.037) compared to those from NSA patients, which were in a positive correlation (r = 0.758, P < 0.001). LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, significantly reduced both autophagy and EET production. EET could trigger immune responses of AECs by inducing interleukin (IL)-6 and IL-8 production from A549 cells and damage airway epithelium by causing A549 cell death.

CONCLUSIONS: Eosinophil autophagy and EETs could increase asthma severity by activating (AECs). Therefore, modulation of autophagy may be a new therapeutic approach for SA treatment.