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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1191-1198. Prepublished online as a Blood First Edition Paper on May 8, 2007; DOI 10.1182/blood-2006-11-060103. This Article Full Text (PDF) All Versions of this Article: blood-2006-11-060103v1 110/4/1191    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 Liu, L. Articles by Kubes, P. Search for Related Content PubMed PubMed Citation Articles by Liu, L. Articles by Kubes, P. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 29, 2006 Accepted April 24, 2007 Leukocyte PI3K and PI3K have temporally distinct roles for leukocyte recruitment in vivo Lixin Liu, Kamal D. Puri, Josef M. Penninger, and Paul Kubes* Department of Physiology & Biophysics, Immunology Research Group, University of Calgary, Calgary, Alberta, Canada Calistoga Pharmaceuticals, Inc., Seattle, WA, United States Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna, Austria * Corresponding author; email: pkubes{at}ucalgary.ca. Phosphoinositide 3-kinases (PI3K) have been considered important in leukocyte motility. PI3K, the class IB PI3K, expressed prominently in leukocytes and also in endothelial cells, mediates leukocyte functional responses induced by chemoattractants. To reveal its role in leukocyte recruitment, we used intravital microscopy to directly visualize leukocyte rolling, adhesion and emigration in postcapillary venules in PI3K-deficient (PI3K-/-) mice. We report here that PI3K deficiency had no significant effects on leukocyte rolling flux or rolling velocity and minor effects on adhesion (30-35%) in response to CXC chemokine MIP-2 (CXCL2) or KC (CXCL1). However, leukocyte emigration was severely impaired in PI3K-/- mice in an early (first 90 min) response to MIP-2 or KC. Bone marrow transplanted chimeric mice revealed that this early response was entirely dependent upon PI3K in neutrophils not parenchymal cells (endothelium etc). Identical responses were observed when endogenous chemokine production was induced by TNF; leukocyte emigration was reduced in PI3K-/- mice. More prolonged responses to MIP-2 (for 4-5 h) or TNF (6-8 hrs) were almost entirely PI3K-independent, and largely dependent on PI3K. Our results reveal that leukocyte emigration response to CXC chemokines is entirely dependent upon PI3K or PI3K, but these are non-overlapping, temporally distinct events in inflamed tissues in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Shedding light on class I phosphoinositide 3-kinase activity in endothelium Tara M. Randis, Natalie Diacovo, Jero Calafat, and Thomas G. Diacovo Blood 2008 111: 4827-4828. [Full Text] [PDF] Response: What is the appropriate surgical intervention when imaging? Lixin Liu and Paul Kubes Blood 2008 111: 4828. [Full Text] [PDF] This article has been cited by other articles: 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] M. Niedermeier, B. T. Hennessy, Z. A. Knight, M. Henneberg, J. Hu, A. V. Kurtova, W. G. Wierda, M. J. Keating, K. M. Shokat, and J. A. Burger Isoform-selective phosphoinositide 3'-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach Blood, May 28, 2009; 113(22): 5549 - 5557. [Abstract] [Full Text] [PDF] A. Bagorda and C. A. Parent Eukaryotic chemotaxis at a glance J. Cell Sci., August 15, 2008; 121(16): 2621 - 2624. [Full Text] [PDF] S. M. Kerfoot, G. Andonegui, C. S. Bonder, and L. Liu Exogenous stromal cell-derived factor-1 induces modest leukocyte recruitment in vivo Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2524 - H2534. [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] L. Liu and P. Kubes Response: What is the appropriate surgical intervention when imaging? Blood, May 1, 2008; 111(9): 4828 - 4828. [Full Text] [PDF] E. Chavakis, G. Carmona, C. Urbich, S. Gottig, R. Henschler, J. M. Penninger, A. M. Zeiher, T. Chavakis, and S. Dimmeler Phosphatidylinositol-3-Kinase-{gamma} Is Integral to Homing Functions of Progenitor Cells Circ. Res., April 25, 2008; 102(8): 942 - 949. [Abstract] [Full Text] [PDF] B. Heit, L. Liu, P. Colarusso, K. D. Puri, and P. Kubes PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP J. Cell Sci., January 15, 2008; 121(2): 205 - 214. [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. 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