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Blood, 1 July 2005, Vol. 106, No. 1, pp. 150-157. Prepublished online as a Blood First Edition Paper on March 15, 2005; DOI 10.1182/blood-2005-01-0023. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0023v1 106/1/150    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 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. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Phagocytes Cell Adhesion and Motility Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The role of endothelial PI3K activity in neutrophil trafficking Kamal D. Puri, Teresa A. Doggett, Ching-Yu Huang, Jason Douangpanya, Joel S. Hayflick, Martin Turner, Josef Penninger, and Thomas G. Diacovo From the ICOS Corporation, Bothell, WA; the Department of Pediatrics and the Department of Pathology, Washington University School of Medicine, Saint Louis, MO; Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Cambridge, United Kingdom; and the Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria. Phosphoinositide 3-kinase gamma (PI3K) in neutrophils plays a critical role in the directed migration of these cells into inflamed tissues. In this study, we demonstrate the importance of the endothelial component of PI3K activity relative to its leukocyte counterpart in supporting neutrophil interactions with the inflamed vessel wall. Despite the reconstitution of class-Ib PI3K function in neutrophils of p110–/– mice, we observed a 45% reduction in accumulation of these cells in an acute lung injury model. Mechanistically, this appears to result from a perturbation in selectin-mediated adhesion as manifested by a 70% reduction in wild-type (WT) neutrophil attachment to and 17-fold increase in rolling velocities on p110–/– microvessels in vivo in response to tumor necrosis factor alpha (TNF). This alteration in adhesion was further augmented by a deficiency in p110, suggesting that the activity of both catalytic subunits is required for efficient capture of neutrophils by cytokine-stimulated endothelium. Interestingly, E-selectin–mediated adhesion in p110–/– mice was impaired by more than 95%, but no defect in nuclear factor kappa B (NF-B)–induced gene expression was observed. These findings suggest a previously unrecognized partnership between class-I PI3Ks expressed in leukocytes and endothelium, the combination of which is required for the efficient trafficking of immunocompetent cells to sites of inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A little grease helps the cell to stick Charles S. Abrams Blood 2005 106: 4-5. [Full Text] [PDF] This article has been cited by other articles: R. Heller, Q. Chang, G. Ehrlich, S. N. Hsieh, S. M. Schoenwaelder, P. J. Kuhlencordt, K. T. 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Arnal, J.-P. Salles, et al. Genetic and Pharmacological Targeting of Phosphoinositide 3-Kinase-{gamma} Reduces Atherosclerosis and Favors Plaque Stability by Modulating Inflammatory Processes Circulation, March 11, 2008; 117(10): 1310 - 1317. [Abstract] [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] P. Madeddu, N. Kraenkel, L. S. Barcelos, M. Siragusa, P. Campagnolo, A. Oikawa, A. Caporali, A. Herman, O. Azzolino, L. Barberis, et al. Phosphoinositide 3-Kinase {gamma} Gene Knockout Impairs Postischemic Neovascularization and Endothelial Progenitor Cell Functions Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 68 - 76. [Abstract] [Full Text] [PDF] V. 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