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

Isabel T. Lauredo, Juan R. Sabater, Ashfaq Ahmed, Yelena Botvinnikova, William M. Abraham

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)2298-2304
Number of pages7
JournalJournal of applied physiology
Volume85
Issue number6
DOIs
StatePublished - Dec 1998

Keywords

  • Chemokines
  • Chemotaxis
  • Macrophages
  • Neutrophils
  • Phenazines

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

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    Lauredo, I. T., Sabater, J. R., Ahmed, A., Botvinnikova, Y., & Abraham, W. M. (1998). Mechanism of pyocyanin- and 1-hydroxyphenazine-induced lung neutrophilia in sheep airways. Journal of applied physiology, 85(6), 2298-2304. https://doi.org/10.1152/jappl.1998.85.6.2298