Exposure of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-activated human neutrophils to the Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine is associated with impaired calcium efflux and potentiation of primary granule enzyme release.

摘要: Pyocyanin and 1-hydroxyphenazine (1-hp) are low-molecular-weight phenazine redox pigments produced by Pseudomonas aeruginosa (14). Both present in the sputum of patients infected with this microbial pathogen may contribute to both virulence persistence interfering mucociliary system (20, 41, 42). also inhibits epidermal cell growth (7) lymphocyte proliferation (24), has antibiotic properties against other microorganisms (32), influences acquisition iron P. (6). 1-hp, but not pyocyanin, potentiates release primary granule enzymes myeloperoxidase (MPO) elastase from activated neutrophils vitro (29, 30). This activity, if it is operative vivo, would favor development chronic futile inflammatory responses, resulting inflammation-mediated tissue damage; turn reduce host defenses encourage persistence, leading a self-perpetuating cycle bacterially stimulated, host-mediated damage disease progression (5, 26). Although proinflammatory interactions 1-hp human have been described previously 30), biochemical mechanisms which these achieved elucidated. In study, effects on stimulus-activated increase neutrophil cytosolic free Ca2+ levels, precedes prerequisite for extracellular (16, 18, 23), investigated vitro. addition, we measured levels cyclic AMP (cAMP), second messenger intimately involved maintenance homeostasis excitable nonexcitable cells (15, 31), 1-hp-treated neutrophils.