C. Taggart et al., Increased elastase release by CF neutrophils is mediated by tumor necrosisfactor-alpha and interleukin-8, AM J P-LUNG, 278(1), 2000, pp. L33-L41
Citations number
34
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
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.