SEARCH:   Advanced

Blood, 1 August 2005, Vol. 106, No. 3, pp. 1067-1075. Prepublished online as a Blood First Edition Paper on February 17, 2005; DOI 10.1182/blood-2004-08-3323. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3323v1 106/3/1067    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Serezani, C. H. C. Articles by Peters-Golden, M. Search for Related Content PubMed PubMed Citation Articles by Serezani, C. H. C. Articles by Peters-Golden, M. Related Collections Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase Carlos H. C. Serezani, David M. Aronoff, Sonia Jancar, Peter Mancuso, and Marc Peters-Golden From the Divisions of Infectious Diseases and Pulmonary and Critical Care Medicine, Department of Internal Medicine, Medical School, and Department of Environmental Health Science, School of Public Health, University of Michigan, Ann Arbor, MI; and the Department of Immunology, Institute of Biomedical Science IV, University of São Paulo, São Paulo, Brazil. Leukotrienes (LTs) are lipid mediators that participate in inflammatory diseases and innate immune function. We sought to investigate the importance of LTs in regulating the microbicidal activity of alveolar macrophages (AMs) and the molecular mechanisms by which this occurs. The role of LTs in enhancing AM microbicidal activity was evaluated pharmacologically and genetically using in vitro challenge with Klebsiella pneumoniae. Exogenous LTs increased AM microbicidal activity in a dose- and receptor-dependent manner, and endogenous production of LTs was necessary for optimal killing. Leukotriene B4 (LTB4) was more potent than cysteinyl LTs. An important role for nicotinamide adenine dinucleotide (NADPH) oxidase in LT-induced microbicidal activity was indicated by the fact that bacterial killing was abrogated by the NADPH oxidase inhibitor diphenyleneiodonium (DPI; 10 µM) and in AMs derived from gp91phox-deficient mice. By contrast, LT-induced microbicidal activity was independent of the generation of nitric oxide. LTs increased H2O2 production, and LTB4 was again the more potent agonist. Both classes of LTs elicited translocation of p47phox to the cell membrane, and LTB4 induced phosphorylation of p47phox in a manner dependent on protein kinase C- (PKC-) activity. In addition, the enhancement of microbicidal activity by LTs was also dependent on PKC- activity. Our results demonstrate that LTs, especially LTB4, enhanceAM microbicidal activity through the PKC--dependent activation of NADPH oxidase. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Di Gennaro, E. Kenne, M. Wan, O. Soehnlein, L. Lindbom, and J. Z. Haeggstrom Leukotriene B4-induced changes in vascular permeability are mediated by neutrophil release of heparin-binding protein (HBP/CAP37/azurocidin) FASEB J, June 1, 2009; 23(6): 1750 - 1757. [Abstract] [Full Text] [PDF] S. P. Lee, C. H. Serezani, A. I. Medeiros, M. N. Ballinger, and M. Peters-Golden Crosstalk between Prostaglandin E2 and Leukotriene B4 Regulates Phagocytosis in Alveolar Macrophages via Combinatorial Effects on Cyclic AMP J. Immunol., January 1, 2009; 182(1): 530 - 537. [Abstract] [Full Text] [PDF] M. N. Ballinger, L. L. N. Hubbard, T. R. McMillan, G. B. Toews, M. Peters-Golden, R. Paine III, and B. B. Moore Paradoxical role of alveolar macrophage-derived granulocyte-macrophage colony-stimulating factor in pulmonary host defense post-bone marrow transplantation Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L114 - L122. [Abstract] [Full Text] [PDF] C. H. Serezani, J. Chung, M. N. Ballinger, B. B. Moore, D. M. Aronoff, and M. Peters-Golden Prostaglandin E2 Suppresses Bacterial Killing in Alveolar Macrophages by Inhibiting NADPH Oxidase Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 562 - 570. [Abstract] [Full Text] [PDF] C. M. Peres, D. M. Aronoff, C. H. Serezani, N. Flamand, L. H. Faccioli, and M. Peters-Golden Specific Leukotriene Receptors Couple to Distinct G Proteins to Effect Stimulation of Alveolar Macrophage Host Defense Functions J. Immunol., October 15, 2007; 179(8): 5454 - 5461. [Abstract] [Full Text] [PDF] M. A. Nardi, Y. Gor, S. J. Feinmark, F. Xu, and S. Karpatkin Platelet particle formation by anti GPIIIa49-66 Ab, Ca2+ ionophore A23187, and phorbol myristate acetate is induced by reactive oxygen species and inhibited by dexamethasone blockade of platelet phospholipase A2, 12-lipoxygenase, and NADPH oxidase Blood, September 15, 2007; 110(6): 1989 - 1996. [Abstract] [Full Text] [PDF] M. Wan, A. Sabirsh, A. Wetterholm, B. Agerberth, and J. Z. Haeggstrom Leukotriene B4 triggers release of the cathelicidin LL-37 from human neutrophils: novel lipid-peptide interactions in innate immune responses FASEB J, September 1, 2007; 21(11): 2897 - 2905. [Abstract] [Full Text] [PDF] W. J. Piotrowski, A. Antczak, J. Marczak, A. Nawrocka, Z. Kurmanowska, and P. Gorski Eicosanoids in Exhaled Breath Condensate and BAL Fluid of Patients With Sarcoidosis Chest, August 1, 2007; 132(2): 589 - 596. [Abstract] [Full Text] [PDF] J. Lattin, D. A. Zidar, K. Schroder, S. Kellie, D. A. Hume, and M. J. Sweet G-protein-coupled receptor expression, function, and signaling in macrophages J. Leukoc. Biol., July 1, 2007; 82(1): 16 - 32. [Abstract] [Full Text] [PDF] D. M. Aronoff, C. M. Peres, C. H. Serezani, M. N. Ballinger, J. K. Carstens, N. Coleman, B. B. Moore, R. S. Peebles, L. H. Faccioli, and M. Peters-Golden Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities J. Immunol., February 1, 2007; 178(3): 1628 - 1634. [Abstract] [Full Text] [PDF] M. N. Ballinger, D. M. Aronoff, T. R. McMillan, K. R. Cooke, K. Olkiewicz, G. B. Toews, M. Peters-Golden, and B. B. Moore Critical Role of Prostaglandin E2 Overproduction in Impaired Pulmonary Host Response following Bone Marrow Transplantation J. Immunol., October 15, 2006; 177(8): 5499 - 5508. [Abstract] [Full Text] [PDF] C. H. Serezani, J. H. Perrela, M. Russo, M. Peters-Golden, and S. Jancar Leukotrienes Are Essential for the Control of Leishmania amazonensis Infection and Contribute to Strain Variation in Susceptibility. J. Immunol., September 1, 2006; 177(5): 3201 - 3208. [Abstract] [Full Text] [PDF] M. N. Ballinger, R. Paine III, C. H. C. Serezani, D. M. Aronoff, E. S. Choi, T. J. Standiford, G. B. Toews, and B. B. Moore Role of Granulocyte Macrophage Colony-Stimulating Factor during Gram-Negative Lung Infection with Pseudomonas aeruginosa Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 766 - 774. [Abstract] [Full Text] [PDF] P. Mancuso, G. B. Huffnagle, M. A. Olszewski, J. Phipps, and M. Peters-Golden Leptin Corrects Host Defense Defects after Acute Starvation in Murine Pneumococcal Pneumonia Am. J. Respir. Crit. Care Med., January 15, 2006; 173(2): 212 - 218. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020