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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3474-3482. Prepublished online as a Blood First Edition Paper on July 21, 2005; DOI 10.1182/blood-2005-03-1327. This Article Full Text (PDF) All Versions of this Article: 2005-03-1327v1 106/10/3474    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kemp, T. J Articles by Griffith, T. S Search for Related Content PubMed PubMed Citation Articles by Kemp, T. J Articles by Griffith, T. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 31, 2005 Accepted July 8, 2005 Neutrophil stimulation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) results in the release of functional soluble TRAIL/Apo-2L Troy J Kemp, Aaron T Ludwig, James K Earel, Jill M Moore, Rebecca L VanOosten, Bonita Moses, Kevin Leidal, William M Nauseef, and Thomas S Griffith* Department of Urology, University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA Department of Urology, University of Iowa, Iowa City, IA, USA Department of Internal Medicine, Inflammation Program, University of Iowa, Iowa City, IA, USA Department of Internal Medicine, Inflammation Program, University of Iowa, Iowa City, IA, USA; Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, USA; Veterans Affairs Medical Center, Iowa City, IA, USA * Corresponding author; email: thomas-griffith{at}uiowa.edu. Mycobacterium bovis BCG has been used to treat bladder cancer for almost 30 years; however, the effector mechanism of the BCG-induced antitumor response remains enigmatic. Most BCG research has focused on the mononuclear cell infiltrate, but growing evidence supports a role for neutrophils in the antitumor response. Previously, we demonstrated increased urinary TNF-related apoptosis inducing ligand (TRAIL/Apo-2L) levels from BCG-responsive patients compared to nonresponders. Interestingly, neutrophils isolated from the urine expressed TRAIL/Apo-2L, leading us to investigate the neutrophil response to BCG. BCG-stimulated neutrophils expressed surface bound and released functional soluble TRAIL/Apo-2L. Whereas neither IFN- nor IFN- directly induced TRAIL/Apo2L expression by neutrophils, IFN- did stimulate TRAIL gene transcription, and IFN-primed neutrophils contained and released more TRAIL/Apo-2L after BCG stimulation than did unprimed neutrophils. In unstimulated neutrophils TRAIL/Apo-2L was present predominantly in the azurophilic granules and plasma membrane-enriched/secretory granule fraction. Finally, we observed that killed BCG, TLR2 and 4 agonists, and a M. tuberculosis cell wall fraction were each capable of inducing the release of soluble TRAIL/Apo-2L from neutrophils. These results further characterize the potential role neutrophils may play in initiating the antitumor response described with BCG treatment for superficial bladder cancer. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Kamat, S. T. Tharakan, B. Sung, and B. B. Aggarwal Curcumin Potentiates the Antitumor Effects of Bacillus Calmette-Guerin against Bladder Cancer through the Downregulation of NF-{kappa}B and Upregulation of TRAIL Receptors Cancer Res., December 1, 2009; 69(23): 8958 - 8966. [Abstract] [Full Text] [PDF] M. De Cesare, C. Calcaterra, G. Pratesi, L. Gatti, F. Zunino, S. Menard, and A. Balsari Eradication of Ovarian Tumor Xenografts by Locoregional Administration of Targeted Immunotherapy Clin. Cancer Res., September 1, 2008; 14(17): 5512 - 5518. [Abstract] [Full Text] [PDF] M. P. Simons, K. G. Leidal, W. M. Nauseef, and T. S. Griffith TNF-related apoptosis-inducing ligand (TRAIL) is expressed throughout myeloid development, resulting in a broad distribution among neutrophil granules J. Leukoc. Biol., March 1, 2008; 83(3): 621 - 629. [Abstract] [Full Text] [PDF] M. P. Simons, J. M. Moore, T. J. Kemp, and T. S. Griffith Identification of the Mycobacterial Subcomponents Involved in the Release of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand from Human Neutrophils Infect. Immun., March 1, 2007; 75(3): 1265 - 1271. [Abstract] [Full Text] [PDF] J. M. Challacombe, A. Suhrbier, P. G. Parsons, B. Jones, P. Hampson, D. Kavanagh, G. E. Rainger, M. Morris, J. M. Lord, T. T. T. Le, et al. Neutrophils Are a Key Component of the Antitumor Efficacy of Topical Chemotherapy with Ingenol-3-Angelate J. Immunol., December 1, 2006; 177(11): 8123 - 8132. [Abstract] [Full Text] [PDF] H. Suttmann, J. Riemensberger, G. Bentien, D. Schmaltz, M. Stockle, D. Jocham, A. Bohle, and S. Brandau Neutrophil Granulocytes Are Required for Effective Bacillus Calmette-Guerin Immunotherapy of Bladder Cancer and Orchestrate Local Immune Responses Cancer Res., August 15, 2006; 66(16): 8250 - 8257. [Abstract] [Full Text] [PDF] M. A. Cassatella On the production of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2L) by human neutrophils J. Leukoc. Biol., June 1, 2006; 79(6): 1140 - 1149. [Abstract] [Full Text] [PDF]

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