Increased elastase release by CF neutrophils is mediated by tumor necrosisfactor-alpha and interleukin-8

Increased elastase release by CF neutrophils is mediated by tumor necrosis factor-alpha and interleukin-8. Am. J. Physiol. Lung Cell. Mot. Physiol. 27 8: L33-L41, 2000.-Cystic fibrosis (CF) is a lethal, hereditary disorder cha racterized by a neutrophil-dominated inflammation of the lung. We sought to determine whether neutrophils from individuals with CF release more neutro phil elastase (NE) than neutrophils from normal subjects. Our results showe d that peripheral blood neutrophils (PBNs) from normal subjects and individ uals with CF contained similar amounts of NE, but after preincubation with CF bronchoalveolar lavage (BAL) fluid, significantly more NE was released b y CF PBNs, a release that was amplified further by incubation with opsonize d Escherichia coli. To determine which components of CF BAL fluid stimulate d this excessive NE release from CF PBNs, we repeated the experiments after neutralization or immunoprecipitation of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 in CF BAL fluid. We found that subsequent NE releas e from CF PBNs was reduced significantly when TNF-alpha and IL-8 were remov ed from CF BAL fluid. When TNF-alpha: and IL-8 were used as activating stim uli, CF PBNs released significantly greater amounts of NE compared with PBN s from control subjects and individuals with bronchiectasis. These results indicate that CF PBNs respond abnormally to TNF-alpha and IL-8 in CF BAL fl uid and react to opsonized bacteria by releasing more NE. This may help exp lain the increased NE burden seen in this condition.