SEARCH:   Advanced

Blood, 1 May 2004, Vol. 103, No. 9, pp. 3448-3456. Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-05-1667. This Article Full Text (PDF) All Versions of this Article: 2003-05-1667v1 103/9/3448    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 Puri, K. D Articles by Diacovo, T. G Search for Related Content PubMed PubMed Citation Articles by Puri, K. D Articles by Diacovo, T. G Social Bookmarking                   What's this? Submitted May 27, 2003 Accepted January 3, 2004 Mechanisms and implications of phosphoinositide 3-kinase in promoting neutrophil trafficking into inflamed tissue Kamal D Puri, Teresa A Doggett, Jason Douangpanya, Yonghao Hou, William T Tino, Timothy Wilson, Thomas Graf, Elizabeth Clayton, Martin Turner, Joel S Hayflick, and Thomas G Diacovo* ICOS Corporation, Bothell, WA, USA Department of Pediatrics, Washington University and St. Louis Children's Hospital, St. Louis, MO, USA Department of Pathology, Washington University, St. Louis, MO, USA Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, United Kingdom Department of Pediatrics, Washington University and St. Louis Children's Hospital, St. Louis, MO, USA; Department of Pathology, Washington University, St. Louis, MO, USA * Corresponding author; email: diacovo_t{at}kids.wustl.edu. The phosphoinositide 3-kinase (PI3K) catalytic subunit p110 is expressed in neutrophils and is thought to play a role in their accumulation at sites of inflammation by contributing solely to chemoattractant-directed migration. We report here that p110 is present in endothelium and participates in neutrophil trafficking by modulating the proadhesive state of these cells in response to TNF. Specifically, administration of selective inhibitor of PI3K, IC87114, to animals reduced neutrophil tethering to and increased rolling velocities on cytokine-activated microvessels in a manner similar to that observed in mice deficient in p110. These results were confirmed in vitro as inhibition of this isoform in endothelium, but not in neutrophils, diminished cell attachment in flow. A role for PI3K in TNF-induced signaling is demonstrated by a reduction in Akt-phosphorylation and PDK1 enzyme activity upon treatment of this cell type with IC87114. p110 expressed in neutrophils also contributes to trafficking as demonstrated by the impaired movement of these cells across inflamed venulae in animals in which this catalytic subunit was blocked or genetically deleted, results corroborated in transwell migration assays. Thus, PI3K may be a reasonable therapeutic target in specific inflammatory conditions as blockade of its activity reduces neutrophil influx into tissues by diminishing their attachment to and migration across vascular endothelium. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. A. Durand, K. Hartvigsen, L. Fogelstrand, S. Kim, S. Iritani, B. Vanhaesebroeck, J. L. Witztum, K. D. Puri, and M. R. Gold Phosphoinositide 3-Kinase p110{delta} Regulates Natural Antibody Production, Marginal Zone and B-1 B Cell Function, and Autoantibody Responses J. Immunol., November 1, 2009; 183(9): 5673 - 5684. [Abstract] [Full Text] [PDF] B. Sarraj, S. Massberg, Y. Li, A. Kasorn, K. Subramanian, F. Loison, L. E. Silberstein, U. von Andrian, and H. R. Luo Myeloid-Specific Deletion of Tumor Suppressor PTEN Augments Neutrophil Transendothelial Migration during Inflammation J. Immunol., June 1, 2009; 182(11): 7190 - 7200. [Abstract] [Full Text] [PDF] F. Morello, A. Perino, and E. Hirsch Phosphoinositide 3-kinase signalling in the vascular system Cardiovasc Res, May 1, 2009; 82(2): 261 - 271. [Abstract] [Full Text] [PDF] A. Saudemont, F. Garcon, H. Yadi, M. Roche-Molina, N. Kim, A. Segonds-Pichon, A. Martin-Fontecha, K. Okkenhaug, and F. Colucci p110{gamma} and p110{delta} isoforms of phosphoinositide 3-kinase differentially regulate natural killer cell migration in health and disease PNAS, April 7, 2009; 106(14): 5795 - 5800. [Abstract] [Full Text] [PDF] J. A. Marwick, G. Caramori, C. S. Stevenson, P. Casolari, E. Jazrawi, P. J. Barnes, K. Ito, I. M. Adcock, P. A. Kirkham, and A. Papi Inhibition of PI3K{delta} Restores Glucocorticoid Function in Smoking-induced Airway Inflammation in Mice Am. J. Respir. Crit. Care Med., April 1, 2009; 179(7): 542 - 548. [Abstract] [Full Text] [PDF] C. Gamell, N. Osses, R. Bartrons, T. Ruckle, M. Camps, J. L. Rosa, and F. Ventura BMP2 induction of actin cytoskeleton reorganization and cell migration requires PI3-kinase and Cdc42 activity J. Cell Sci., December 1, 2008; 121(23): 3960 - 3970. [Abstract] [Full Text] [PDF] S. Konrad, S. R. Ali, K. Wiege, S. N. Syed, L. Engling, R. P. Piekorz, E. Hirsch, B. Nurnberg, R. E. Schmidt, and J. E. Gessner Phosphoinositide 3-Kinases {gamma} and {delta}, Linkers of Coordinate C5a Receptor-Fc{gamma} Receptor Activation and Immune Complex-induced Inflammation J. Biol. Chem., November 28, 2008; 283(48): 33296 - 33303. [Abstract] [Full Text] [PDF] T. M. Randis, N. Diacovo, J. Calafat, and T. G. Diacovo Shedding light on class I phosphoinositide 3-kinase activity in endothelium Blood, May 1, 2008; 111(9): 4827 - 4828. [Full Text] [PDF] K. Ali, M. Camps, W. P. Pearce, H. Ji, T. Ruckle, N. Kuehn, C. Pasquali, C. Chabert, C. Rommel, and B. Vanhaesebroeck Isoform-Specific Functions of Phosphoinositide 3-Kinases: p110{delta} but Not p110{gamma} Promotes Optimal Allergic Responses In Vivo J. Immunol., February 15, 2008; 180(4): 2538 - 2544. [Abstract] [Full Text] [PDF] M. L. Janas, D. Hodson, Z. Stamataki, S. Hill, K. Welch, L. Gambardella, L. C. Trotman, P. P. Pandolfi, E. Vigorito, and M. Turner The Effect of Deleting p110{delta} on the Phenotype and Function of PTEN-Deficient B Cells J. Immunol., January 15, 2008; 180(2): 739 - 746. [Abstract] [Full Text] [PDF] V. Pinho, R. de Castro Russo, F. A. Amaral, L. P. de Sousa, M. M. Barsante, D. G. de Souza, J. C. Alves-Filho, D. C. Cara, J. S. Hayflick, C. Rommel, et al. Tissue- and Stimulus-Dependent Role of Phosphatidylinositol 3-Kinase Isoforms for Neutrophil Recruitment Induced by Chemoattractants In Vivo J. Immunol., December 1, 2007; 179(11): 7891 - 7898. [Abstract] [Full Text] [PDF] M. Nakhaei-Nejad, A. M. Hussain, Q.-X. Zhang, and A. G. Murray Endothelial PI 3-kinase activity regulates lymphocyte diapedesis Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3608 - H3616. [Abstract] [Full Text] [PDF] H. Ji, F. Rintelen, C. Waltzinger, D. Bertschy Meier, A. Bilancio, W. Pearce, E. Hirsch, M. P. Wymann, T. Ruckle, M. Camps, et al. Inactivation of PI3K{gamma} and PI3K{delta} distorts T-cell development and causes multiple organ inflammation Blood, October 15, 2007; 110(8): 2940 - 2947. [Abstract] [Full Text] [PDF] H.-P. Yu, Y.-C. Hsieh, T. Suzuki, M. A. Choudhry, M. G. Schwacha, K. I. Bland, and I. H. Chaudry Mechanism of the nongenomic effects of estrogen on intestinal myeloperoxidase activity following trauma-hemorrhage: up-regulation of the PI-3K/Akt pathway J. Leukoc. Biol., September 1, 2007; 82(3): 774 - 780. [Abstract] [Full Text] [PDF] L. Liu, K. D. Puri, J. M. Penninger, and P. Kubes Leukocyte PI3K{gamma} and PI3K{delta} have temporally distinct roles for leukocyte recruitment in vivo Blood, August 15, 2007; 110(4): 1191 - 1198. [Abstract] [Full Text] [PDF] C. D. Wrann, N. A. Tabriz, T. Barkhausen, A. Klos, M. van Griensven, H. C. Pape, D. O. Kendoff, R. Guo, P. A. Ward, C. Krettek, et al. The Phosphatidylinositol 3-Kinase Signaling Pathway Exerts Protective Effects during Sepsis by Controlling C5a-Mediated Activation of Innate Immune Functions J. Immunol., May 1, 2007; 178(9): 5940 - 5948. [Abstract] [Full Text] [PDF] K. Ito, G. Caramori, and I. M. Adcock Therapeutic Potential of Phosphatidylinositol 3-Kinase Inhibitors in Inflammatory Respiratory Disease J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 1 - 8. [Abstract] [Full Text] [PDF] C.-W. Lee, C.-C. Lin, W.-N. Lin, K.-C. Liang, S.-F. Luo, C.-B. Wu, S.-W. Wang, and C.-M. Yang TNF-{alpha} induces MMP-9 expression via activation of Src/EGFR, PDGFR/PI3K/Akt cascade and promotion of NF-{kappa}B/p300 binding in human tracheal smooth muscle cells Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L799 - L812. [Abstract] [Full Text] [PDF] C. Sciorati, B. G. Galvez, S. Brunelli, E. Tagliafico, S. Ferrari, G. Cossu, and E. Clementi Ex vivo treatment with nitric oxide increases mesoangioblast therapeutic efficacy in muscular dystrophy J. Cell Sci., December 15, 2006; 119(24): 5114 - 5123. [Abstract] [Full Text] [PDF] D. F. Smith, T. L. Deem, A. C. Bruce, J. Reutershan, D. Wu, and K. Ley Leukocyte phosphoinositide-3 kinase {gamma} is required for chemokine-induced, sustained adhesion under flow in vivo J. Leukoc. Biol., December 1, 2006; 80(6): 1491 - 1499. [Abstract] [Full Text] [PDF] J. J. Zhao, H. Cheng, S. Jia, L. Wang, O. V. Gjoerup, A. Mikami, and T. M. Roberts The p110{alpha} isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation PNAS, October 31, 2006; 103(44): 16296 - 16300. [Abstract] [Full Text] [PDF] T. Minami, M. Miura, W. C. Aird, and T. Kodama Thrombin-induced Autoinhibitory Factor, Down Syndrome Critical Region-1, Attenuates NFAT-dependent Vascular Cell Adhesion Molecule-1 Expression and Inflammation in the Endothelium J. Biol. Chem., July 21, 2006; 281(29): 20503 - 20520. [Abstract] [Full Text] [PDF] I. Boulven, S. Levasseur, S. Marois, G. Pare, E. Rollet-Labelle, and P. H. Naccache Class IA Phosphatidylinositide 3-Kinases, rather than p110{gamma}, Regulate Formyl-Methionyl-Leucyl-Phenylalanine-Stimulated Chemotaxis and Superoxide Production in Differentiated Neutrophil-Like PLB-985 Cells. J. Immunol., June 15, 2006; 176(12): 7621 - 7627. [Abstract] [Full Text] [PDF] C. Bonnans, K. Fukunaga, R. Keledjian, N. A. Petasis, and B. D. Levy Regulation of phosphatidylinositol 3-kinase by polyisoprenyl phosphates in neutrophil-mediated tissue injury J. Exp. Med., April 17, 2006; 203(4): 857 - 863. [Abstract] [Full Text] [PDF] B. W. LeBlanc, J. E. Albina, and J. S. Reichner The effect of PGG-{beta}-glucan on neutrophil chemotaxis in vivo J. Leukoc. Biol., April 1, 2006; 79(4): 667 - 675. [Abstract] [Full Text] [PDF] K. S. Lee, H. K. Lee, J. S. Hayflick, Y. C. Lee, and K. D. Puri Inhibition of phosphoinositide 3-kinase {delta} attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model FASEB J, March 1, 2006; 20(3): 455 - 465. [Abstract] [Full Text] [PDF] T. G. Diacovo, A. L. Blasius, T. W. Mak, M. Cella, and M. Colonna Adhesive mechanisms governing interferon-producing cell recruitment into lymph nodes J. Exp. Med., September 6, 2005; 202(5): 687 - 696. [Abstract] [Full Text] [PDF] D. A. Fruman Bursting with PIP3 Blood, August 15, 2005; 106(4): 1139 - 1140. [Full Text] [PDF] A. M. Condliffe, K. Davidson, K. E. Anderson, C. D. Ellson, T. Crabbe, K. Okkenhaug, B. Vanhaesebroeck, M. Turner, L. Webb, M. P. Wymann, et al. Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils Blood, August 15, 2005; 106(4): 1432 - 1440. [Abstract] [Full Text] [PDF] K. D. Puri, T. A. Doggett, C.-Y. Huang, J. Douangpanya, J. S. Hayflick, M. Turner, J. Penninger, and T. G. Diacovo The role of endothelial PI3K{gamma} activity in neutrophil trafficking Blood, July 1, 2005; 106(1): 150 - 157. [Abstract] [Full Text] [PDF] B. B. Rubin, G. P. Downey, A. Koh, N. Degousee, F. Ghomashchi, L. Nallan, E. Stefanski, D. W. Harkin, C. Sun, B. P. Smart, et al. Cytosolic Phospholipase A2-{alpha} Is Necessary for Platelet-activating Factor Biosynthesis, Efficient Neutrophil-mediated Bacterial Killing, and the Innate Immune Response to Pulmonary Infection: cPLA2-{alpha} DOES NOT REGULATE NEUTROPHIL NADPH OXIDASE ACTIVITY J. Biol. Chem., March 4, 2005; 280(9): 7519 - 7529. [Abstract] [Full Text] [PDF] I. E. Konstantinov, S. Arab, R. K. Kharbanda, J. Li, M. M. H. Cheung, V. Cherepanov, G. P. Downey, P. P. Liu, E. Cukerman, J. G. Coles, et al. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans Physiol Genomics, September 16, 2004; 19(1): 143 - 150. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020