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Blood, 1 July 2005, Vol. 106, No. 1, pp. 103-109. Prepublished online as a Blood First Edition Paper on March 15, 2005; DOI 10.1182/blood-2004-10-4041. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-4041v1 106/1/103    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 Munugalavadla, V. Articles by Kapur, R. Search for Related Content PubMed PubMed Citation Articles by Munugalavadla, V. Articles by Kapur, R. Related Collections Hematopoiesis and Stem Cells Phagocytes Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS p85 subunit of class IA PI-3 kinase is crucial for macrophage growth and migration Veerendra Munugalavadla, Jovencio Borneo, David A. Ingram, and Reuben Kapur From the Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN. Macrophages play an essential role in defending against invading pathogens by migrating to the sites of infection, removing apoptotic cells, and secreting inflammatory cytokines. The molecular mechanisms whereby macrophages regulate these processes are poorly understood. Using bone marrow–derived macrophages (BMMs) deficient in the expression of p85-subunit of class IA phosphatidylinositol 3 (PI-3) kinase, we demonstrate 50% reduction in proliferation in response to macrophage–colony-stimulating factor (M-CSF) as well as granulocyte macrophage–colony-stimulating factor (GM-CSF) compared with wild-type controls. Furthermore, p85–/– BMMs demonstrate a significant reduction in migration in a wound-healing assay compared with wild-type controls. The reduction in migration due to p85 deficiency in BMMs is associated with reduced adhesion and directed migration on fibronectin and vascular cell adhesion molecule-1. In addition, deficiency of p85 in BMMs also results in defective phagocytosis of sheep red blood cells. Biochemically, loss of p85 in BMMs results in reduced activation of Akt and Rac, but not Erk (extracellular signal-related kinase) mitogen-activated protein (MAP) kinase. Taken together, our results provide genetic evidence for the importance of p85 in regulating both actin- and growth-based functions in macrophages, and provide a potential therapeutic target for the treatment of diseases involving macrophages, including 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. Cheung, M. Malik, V. Ravyn, B. Tomkowicz, A. Ptasznik, and R. G. Collman An arrestin-dependent multi-kinase signaling complex mediates MIP-1{beta}/CCL4 signaling and chemotaxis of primary human macrophages J. Leukoc. Biol., October 1, 2009; 86(4): 833 - 845. [Abstract] [Full Text] [PDF] C. S. Boosani, N. Nalabothula, V. Munugalavadla, D. Cosgrove, V. G. Keshamoun, N. Sheibani, and A. Sudhakar FAK and p38-MAP Kinase-Dependent Activation of Apoptosis and Caspase-3 in Retinal Endothelial Cells by {alpha}1(IV)NC1 Invest. Ophthalmol. Vis. Sci., October 1, 2009; 50(10): 4567 - 4575. [Abstract] [Full Text] [PDF] V. Munugalavadla, S. Vemula, E. C. Sims, S. Krishnan, S. Chen, J. Yan, H. Li, P. J. Niziolek, C. Takemoto, A. G. Robling, et al. The p85{alpha} Subunit of Class IA Phosphatidylinositol 3-Kinase Regulates the Expression of Multiple Genes Involved in Osteoclast Maturation and Migration Mol. Cell. Biol., December 1, 2008; 28(23): 7182 - 7198. [Abstract] [Full Text] [PDF] L. N. Jackson, S. D. Larson, S. R. Silva, P. G. Rychahou, L. A. Chen, S. Qiu, S. Rajaraman, and B. M. Evers PI3K/Akt activation is critical for early hepatic regeneration after partial hepatectomy Am J Physiol Gastrointest Liver Physiol, June 1, 2008; 294(6): G1401 - G1410. [Abstract] [Full Text] [PDF] J. P. Luyendyk, G. A. Schabbauer, M. Tencati, T. Holscher, R. Pawlinski, and N. Mackman Genetic Analysis of the Role of the PI3K-Akt Pathway in Lipopolysaccharide-Induced Cytokine and Tissue Factor Gene Expression in Monocytes/Macrophages J. Immunol., March 15, 2008; 180(6): 4218 - 4226. [Abstract] [Full Text] [PDF] K. A. Horan, K.-i. Watanabe, A. M. Kong, C. G. Bailey, J. E. J. Rasko, T. Sasaki, and C. A. Mitchell Regulation of Fc{gamma}R-stimulated phagocytosis by the 72-kDa inositol polyphosphate 5-phosphatase: SHIP1, but not the 72-kDa 5-phosphatase, regulates complement receptor 3 mediated phagocytosis by differential recruitment of these 5-phosphatases to the phagocytic cup Blood, December 15, 2007; 110(13): 4480 - 4491. [Abstract] [Full Text] [PDF] M. P. Matheu, J. A. Deane, I. Parker, D. A. Fruman, and M. D. Cahalan Class IA Phosphoinositide 3-Kinase Modulates Basal Lymphocyte Motility in the Lymph Node J. Immunol., August 15, 2007; 179(4): 2261 - 2269. [Abstract] [Full Text] [PDF] R. Faccio, S. Takeshita, G. Colaianni, J. Chappel, A. Zallone, S. L. Teitelbaum, and F. P. Ross M-CSF Regulates the Cytoskeleton via Recruitment of a Multimeric Signaling Complex to c-Fms Tyr-559/697/721 J. Biol. Chem., June 29, 2007; 282(26): 18991 - 18999. [Abstract] [Full Text] [PDF] H. K. Bone and M. J. Welham Phosphoinositide 3-kinase signalling regulates early development and developmental haemopoiesis J. Cell Sci., May 15, 2007; 120(10): 1752 - 1762. [Abstract] [Full Text] [PDF] L. S. Haneline, H. White, F.-C. Yang, S. Chen, C. Orschell, R. Kapur, and D. A. Ingram Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive repopulating ability of hematopoietic stem cells in vivo Blood, February 15, 2006; 107(4): 1375 - 1382. [Abstract] [Full Text] [PDF]

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