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Abstract
Cystic fibrosis (CF) lung disease involves chronic bacterial infections, often of Staphylococcus aureus and Pseudomonas aeruginosa, with infiltration of dysfunctional PMNs. Short chain fatty acids (SCFAs) are present at millimolar concentrations in CF sputum as byproducts of anerobic bacterial fermentation. The effect of CF sputum and SCFAs on PMNs has not been well described. The goal of this project was to characterize the effects of CF sputum and SCFAs on the effector functions of PMNs in response to CF clinical isolates of S. aureus and P. aeruginosa. The results show that CF sputum, following previous observations of inhibiting bacterial killing, increases neutrophil extracellular trap (NET) release. Similarly, SCFAs reduce killing, increase NET release, and inhibit superoxide production. Overall, this is consistent with PMN dysfunction described in the CF lung, characterizes an in vitro model to study CF PMNs, and provides a potential explanation for PMN dysfunction occurring in CF sputum.