Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways

• Published in: Journal of applied physiology (1985) 1998-12, Vol.85 (6), p.2298-2304
• Main Authors: Lauredo, Isabel T, Sabater, Juan R, Ahmed, Ashfaq, Botvinnikova, Yelena, Abraham, William M
• Format: Article
• Language: English
• Subjects: Anatomy & physiology; Animals; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Chemotaxis, Leukocyte - drug effects; Female; Fundamental and applied biological sciences. Psychology; Hydroxyurea - analogs & derivatives; Hydroxyurea - pharmacology; In Vitro Techniques; Inflammation; Interleukin-8 - antagonists & inhibitors; Interleukin-8 - biosynthesis; Leukotriene B4 - antagonists & inhibitors; Leukotriene B4 - biosynthesis; Lung - drug effects; Lung - pathology; Lung - physiopathology; Lungs; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - physiology; Molecular and cellular biology; Neutrophils - drug effects; Neutrophils - pathology; Neutrophils - physiology; Phenazines - toxicity; Pseudomonas aeruginosa; Pseudomonas aeruginosa - pathogenicity; Pyocyanine - toxicity; Respiratory diseases; Sheep
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1998.85.6.2298

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 10 5 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 B 4 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