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and interleukin-8
1 Pulmonary Research Division, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9; and 2 Our Lady's Hospital for Sick Children, Dublin 12, Ireland
Cystic fibrosis (CF)
is a lethal, hereditary disorder characterized by a
neutrophil-dominated inflammation of the lung. We sought to determine
whether neutrophils from individuals with CF release more neutrophil
elastase (NE) than neutrophils from normal subjects. Our results showed
that peripheral blood neutrophils (PBNs) from normal subjects and
individuals with CF contained similar amounts of NE, but after
preincubation with CF bronchoalveolar lavage (BAL) fluid,
significantly more NE was released by CF PBNs, a release that was
amplified further by incubation with opsonized Escherichia
coli. To determine which components of CF BAL fluid stimulated this
excessive NE release from CF PBNs, we repeated the experiments after
neutralization or immunoprecipitation of tumor necrosis factor
(TNF)-
and interleukin (IL)-8 in CF BAL fluid. We found that
subsequent NE release from CF PBNs was reduced significantly when
TNF- and IL-8 were removed from CF BAL fluid. When TNF- and IL-8
were used as activating stimuli, CF PBNs released significantly greater
amounts of NE compared with PBNs from control subjects and individuals
with bronchiectasis. These results indicate that CF PBNs respond
abnormally to TNF- and IL-8 in CF BAL fluid and react to opsonized
bacteria by releasing more NE. This may help explain the increased NE
burden seen in this condition.
secretion; inflammation; proteases; cytokines
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