Pseudomonas aeruginosa exotoxin A primes human monocyte oxidative burst response in vitro.

Modulation of the oxidative burst responsiveness of human blood monocytes and neutrophils after incubation with purified exotoxin A from Pseudomonas aeruginosa was studied in a lucigenin- and luminol-enhanced chemiluminescence system. Exotoxin A alone caused a dose-dependent stimulation of monocyte chemiluminescence responses, whereas neutrophil responses were inconsistent. Preincubation of monocytes with exotoxin A primed the cells for a significantly higher oxidative burst response when N-f-methionyl-leucyl-phenylalanine (fMLP) was used as a secondary stimulus, especially in the lucigenin-enhanced system. Heat-treatment at 100 degrees C for 15 min completely abolished the priming activity of the exotoxin A preparation. These findings demonstrate that exotoxin A modulates monocyte responsiveness in the chemiluminescence assay and suggest that increased release of toxic oxygen radicals from mononuclear phagocytes may contribute to the tissue damage in lungs with chronic P. aeruginosa infections.