title: Enhanced release of elastase and oxidative inactivation of alpha-1-protease inhibitor by stimulated human neutrophils exposed to Pseudomonas aeruginosa pigment 1-hydroxyphenazine.
abstract: The in vitro effects of the Pseudomonas aeruginosa-derived phenazine pigments pyocyanin and 1-hydroxyphenazine (1-hp) on neutrophil elastase release and myeloperoxidase-induced inactivation of alpha-1-protease inhibitor (alpha 1-PI) were investigated. 1-hp (6-25 microM), but not pyocyanin, caused a dose-dependent enhancement of elastase release by FMLP:cytochalasin B (CB)-activated human neutrophils. 1-hp (0.78-6.25 microM) also increased the oxidative inactivation of the elastase inhibitory capacity of alpha 1-PI exposed to FMLP:CB-activated neutrophils. Methionine, a scavenger of hypochlorous acid, completely protected alpha 1-PI from inactivation by stimulated neutrophils in the presence or absence of 1-hp. Similar protective effects were observed with sodium azide, an inhibitor of myeloperoxidase. P. aeruginosa-derived 1-hp may promote an elastase-antielastase imbalance in vivo by increasing the release of neutrophil elastase and by enhancing the oxidative inactivation of alpha 1-PI, thereby contributing to the development of tissue destruction in P. aeruginosa-infected patients.
authors.affiliation: Department of Immunology, University of Pretoria, South Africa.
authors.forename: G J
authors.initials: GJ
authors.lastname: Ras
authors.forename: A J
authors.initials: AJ
authors.lastname: Theron
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: G W
authors.initials: GW
authors.lastname: Taylor
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.forename: P J
authors.initials: PJ
authors.lastname: Cole
authors.forename: C A
authors.initials: CA
authors.lastname: van der Merwe
mesh_terms: D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D010586:Phagocytes / Q000502:physiology; D010619:Phenazines / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D011710:Pyocyanine / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D010619:Phenazines; D000515:alpha 1-Antitrypsin; C050093:1-hydroxyphenazine; D011710:Pyocyanine; D009195:Peroxidase; D010196:Pancreatic Elastase