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Division of Pulmonary Disease, Mount Sinai Medical Center, Miami Beach, Florida 33140
Pyocyanin (Pyo)
and 1-hydroxyphenazine (1-HP) are extracellular products of
Pseudomonas aeruginosa. To test
whether these products were capable of producing an inflammatory
response in the airways, combinations of Pyo and 1-HP at concentrations
of 10
4 and
105 M were instilled into
sheep airways, and indexes of inflammation were assessed by
bronchoalveolar lavage (BAL) 24 h later. Challenge with the phenazines
caused a significant dose-dependent increase in the number of cells and
neutrophils recovered by BAL. Control challenges produced no such
changes. The lung neutrophilia was accompanied by an increased
concentration of albumin in BAL. The increases in BAL neutrophils and
albumin could be blocked by treating the sheep with the 5-lipoxygenase
inhibitor zileuton. Neither 1-HP nor Pyo was chemotactic to neutrophils
when tested in vitro, but when alveolar macrophages (AM) were cultured
in vitro in the presence of both Pyo and 1-HP (1 µM), the
supernatants caused neutrophil chemotaxis. Analysis of AM culture
supernatants incubated with the combination of pigments showed
significant increases in leukotriene
B4 and interleukin-8, and blocking
these mediators separately or together reduced AM supernatant-induced
neutrophil chemotaxis. We conclude that local instillation of Pyo and
1-HP can initiate an inflammatory response in the airways of sheep in
vivo. This effect can be explained, in part, by the release of
chemotactic factors produced by AM.
phenazines; chemotaxis; chemokines; macrophages; neutrophils
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