| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Respiratory Medicine Unit and
Infectious Diseases Unit, Division of Genomic Medicine and
Institute of Child Health, University of Sheffield Medical School, Sheffield, United Kingdom; and
Division on Clinical Pharmacology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
Pseudomonas aeruginosa colonizes and infects human tissues, although the mechanisms by which the organism evades the normal, predominantly neutrophilic, host defenses are unclear. Phenazine products of P. aeruginosa can induce death in Caenorhabditis elegans. We hypothesized that phenazines induce death of human neutrophils, and thus impair neutrophil-mediated bacterial killing. We investigated the effects of two phenazines, pyocyanin and 1-hydroxyphenazine, upon apoptosis of neutrophils in vitro. Pyocyanin induced a concentration- and time-dependent acceleration of neutrophil apoptosis, with 50 µM pyocyanin causing a 10-fold induction of apoptosis at 5 h (p < 0.001), a concentration that has been documented in sputum from patients colonized with P. aeruginosa. 1-hydroxyphenazine was without effect. In contrast to its rapid induction of neutrophil apoptosis, pyocyanin did not induce significant apoptosis of monocyte-derived macrophages or airway epithelial cells at time points up to 24 h. Comparison of wild-type and phenazine-deleted strains of P. aeruginosa showed a highly significant reduction in neutrophil killing by the phenazine-deleted strain. In clinical isolates of P. aeruginosa pyocyanin production was associated with a proapoptotic effect upon neutrophils in culture. Pyocyanin-induced neutrophil apoptosis was not delayed either by treatment with LPS, a powerfully antiapoptotic bacterial product, or in neutrophils from cystic fibrosis patients. Pyocyanin-induced apoptosis was associated with rapid and sustained generation of reactive oxygen intermediates and subsequent reduction of intracellular cAMP. Treatment of neutrophils with either antioxidants or synthetic cAMP analogues significantly abrogated pyocyanin-induced apoptosis. We conclude that pyocyanin-induced neutrophil apoptosis may be a clinically important mechanism of persistence of P. aeruginosa in human tissue.
This article has been cited by other articles:
|
|
 |
|
  D G Downey, S C Bell, and J S Elborn Neutrophils in cystic fibrosis Thorax, January 1, 2009; 64(1): 81 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. El Solh, M. E. Akinnusi, J. P. Wiener-Kronish, S. V. Lynch, L. A. Pineda, and K. Szarpa Persistent Infection with Pseudomonas aeruginosa in Ventilator-associated Pneumonia Am. J. Respir. Crit. Care Med., September 1, 2008; 178(5): 513 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Prince, S. M. Bianchi, K. M. Vaughan, M. A. Bewley, H. M. Marriott, S. R. Walmsley, G. W. Taylor, D. J. Buttle, I. Sabroe, D. H. Dockrell, et al. Subversion of a Lysosomal Pathway Regulating Neutrophil Apoptosis by a Major Bacterial Toxin, Pyocyanin J. Immunol., March 1, 2008; 180(5): 3502 - 3511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Bianchi, L. R. Prince, K. McPhillips, L. Allen, H. M. Marriott, G. W. Taylor, P. G. Hellewell, I. Sabroe, D. H. Dockrell, P. W. Henson, et al. Impairment of Apoptotic Cell Engulfment by Pyocyanin, a Toxic Metabolite of Pseudomonas aeruginosa Am. J. Respir. Crit. Care Med., January 1, 2008; 177(1): 35 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Naylor, D. Bakstad, M. Biffen, B. Thong, P. Calverley, S. Scott, C. A. Hart, R. J. Moots, and S. W. Edwards Haemophilus influenzae Induces Neutrophil Necrosis: A Role in Chronic Obstructive Pulmonary Disease? Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Dockrell and M. K. B. Whyte Regulation of phagocyte lifespan in the lung during bacterial infection J. Leukoc. Biol., May 1, 2006; 79(5): 904 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nagaoka, H. Tamura, and M. Hirata An Antimicrobial Cathelicidin Peptide, Human CAP18/LL-37, Suppresses Neutrophil Apoptosis via the Activation of Formyl-Peptide Receptor-Like 1 and P2X7. J. Immunol., March 1, 2006; 176(5): 3044 - 3052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Sawatzky, D. A. Willoughby, P. R. Colville-Nash, and A. G. Rossi The Involvement of the Apoptosis-Modulating Proteins ERK 1/2, Bcl-xL and Bax in the Resolution of Acute Inflammation in Vivo Am. J. Pathol., January 1, 2006; 168(1): 33 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A P Watt, J Courtney, J Moore, M Ennis, and J S Elborn Neutrophil cell death, activation and bacterial infection in cystic fibrosis Thorax, August 1, 2005; 60(8): 659 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Sadikot, T. S. Blackwell, J. W. Christman, and A. S. Prince Pathogen-Host Interactions in Pseudomonas aeruginosa Pneumonia Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1209 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Watts, L. Harper, D. Jayne, J. Levy, C. Pusey, C. Savage, D. G. I. Scott, and J. Williams Translational research in autoimmunity: aims of therapy in vasculitis Rheumatology, May 1, 2005; 44(5): 573 - 576. [Full Text] [PDF]
|
|
|
|
|
|
L. Allen, D. H. Dockrell, T. Pattery, D. G. Lee, P. Cornelis, P. G. Hellewell, and M. K. B. Whyte Pyocyanin Production by Pseudomonas aeruginosa Induces Neutrophil Apoptosis and Impairs Neutrophil-Mediated Host Defenses In Vivo J. Immunol., March 15, 2005; 174(6): 3643 - 3649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Prince, L. Allen, E. C. Jones, P. G. Hellewell, S. K. Dower, M. K.B. Whyte, and I. Sabroe The Role of Interleukin-1{beta} in Direct and Toll-Like Receptor 4-Mediated Neutrophil Activation and Survival Am. J. Pathol., November 1, 2004; 165(5): 1819 - 1826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Erickson, J. L. Lines, E. C. Pesci, V. Venturi, and D. G. Storey Pseudomonas aeruginosa relA Contributes to Virulence in Drosophila melanogaster Infect. Immun., October 1, 2004; 72(10): 5638 - 5645. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Lau, H. Ran, F. Kong, D. J. Hassett, and D. Mavrodi Pseudomonas aeruginosa Pyocyanin Is Critical for Lung Infection in Mice Infect. Immun., July 1, 2004; 72(7): 4275 - 4278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Zhang and P. A. Insel The Pro-apoptotic Protein Bim Is a Convergence Point for cAMP/Protein Kinase A- and Glucocorticoid-promoted Apoptosis of Lymphoid Cells J. Biol. Chem., May 14, 2004; 279(20): 20858 - 20865. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ran, D. J. Hassett, and G. W. Lau Human targets of Pseudomonas aeruginosa pyocyanin PNAS, November 25, 2003; 100(24): 14315 - 14320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S Kotecha, R J Mildner, L R Prince, J R Vyas, A E Currie, R A Lawson, and M K B Whyte The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants Thorax, November 1, 2003; 58(11): 961 - 967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Q. O'Malley, K. J. Reszka, G. T. Rasmussen, M. Y. Abdalla, G. M. Denning, and B. E. Britigan The Pseudomonas secretory product pyocyanin inhibits catalase activity in human lung epithelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1077 - L1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tateda, Y. Ishii, M. Horikawa, T. Matsumoto, S. Miyairi, J. C. Pechere, T. J. Standiford, M. Ishiguro, and K. Yamaguchi The Pseudomonas aeruginosa Autoinducer N-3-Oxododecanoyl Homoserine Lactone Accelerates Apoptosis in Macrophages and Neutrophils Infect. Immun., October 1, 2003; 71(10): 5785 - 5793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Sabroe, L. R. Prince, E. C. Jones, M. J. Horsburgh, S. J. Foster, S. N. Vogel, S. K. Dower, and M. K. B. Whyte Selective Roles for Toll-Like Receptor (TLR)2 and TLR4 in the Regulation of Neutrophil Activation and Life Span J. Immunol., May 15, 2003; 170(10): 5268 - 5275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Scaife, Z. Woldehiwet, C. A. Hart, and S. W. Edwards Anaplasma phagocytophilum Reduces Neutrophil Apoptosis In Vivo Infect. Immun., April 1, 2003; 71(4): 1995 - 2001. [Abstract] [Full Text]
|
|
|
|
|
|
Poster presentations Thorax, December 1, 2002; 57(90003): iii48 - 94. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
