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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4080-4087. Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-03-1166. This Article Full Text (PDF) All Versions of this Article: 2004-03-1166v1 104/13/4080    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 Bagga, S. Articles by Boyce, J. A Search for Related Content PubMed PubMed Citation Articles by Bagga, S. Articles by Boyce, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 30, 2004 Accepted August 1, 2004 Lysophosphatidic acid accelerates the development of human mast cells Savita Bagga, Kursteen S Price, Debbie A Lin, Daniel S Friend, K Frank Austen, and Joshua A Boyce* Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, USA Departments of Medicine & Pediatrics, Harvard University, Boston, MA, USA * Corresponding author; email: Jboyce{at}rics.bwh.harvard.edu. Mast cells (MCs) initiate immune responses from mucosal surfaces and perivascular spaces. Stem cell factor (SCF) regulates MC development and viability, but the role of innate serum factors in MC development is unexplored. Cultured cord blood-derived human MCs (hMCs) express mRNA transcripts for all four known receptors for lysophosphatidic acid (LPA), an abundant serum-associated lipid growth factor. In a SCF-dependent serum-free culture system, LPA (2.5-10 µM) increased the total number of hMCs by ~ 10 fold relative to cultures maintained in the absence of LPA under otherwise identical conditions. LPA was comitogenic with SCF, but did not prolong MC survival. LPA-mediated proliferation was blocked by VPC-32179, a competitive antagonist of LPA1 and LPA3 receptors, and by pertussis toxin, and was also attenuated by GW9662, a selective antagonist of peroxisome proliferator-activated receptor (PPAR-). LPA accelerated the acquisition of hMC granules and increased Kit expression. hMCs derived in the presence of LPA were functional, as evidenced by their IgE-dependent histamine release, and by their characteristic responses to IL-3, IL-4, and IL-9 in combination with SCF. Thus, LPA acts through both LPA receptor and PPAR-dependent pathways to accelerate hMC proliferation and differentiation, and modulates their phenotype without providing cytoprotection. LPA could facilitate MC hyperplasia in inflammation associated with either innate or adaptive immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. M. Price, D. Kapitonov, J. Allegood, S. Milstien, C. A. Oskeritzian, and S. Spiegel Sphingosine-1-phosphate induces development of functionally mature chymase-expressing human mast cells from hematopoietic progenitors FASEB J, October 1, 2009; 23(10): 3506 - 3515. [Abstract] [Full Text] [PDF] X. Ye Lysophospholipid signaling in the function and pathology of the reproductive system Hum. Reprod. Update, September 1, 2008; 14(5): 519 - 536. [Abstract] [Full Text] [PDF] D. D. Metcalfe Mast cells and mastocytosis Blood, August 15, 2008; 112(4): 946 - 956. [Abstract] [Full Text] [PDF] S. Paruchuri, Y. Jiang, C. Feng, S. A. Francis, J. Plutzky, and J. A. Boyce Leukotriene E4 Activates Peroxisome Proliferator-activated Receptor {gamma} and Induces Prostaglandin D2 Generation by Human Mast Cells J. Biol. Chem., June 13, 2008; 283(24): 16477 - 16487. [Abstract] [Full Text] [PDF] C.-P. Liu, Y.-C. Kuo, C.-C. Shen, M.-H. Wu, J.-F. Liao, Y.-L. Lin, C.-F. Chen, and W.-J. Tsai (S)-Armepavine inhibits human peripheral blood mononuclear cell activation by regulating Itk and PLC{gamma} activation in a PI-3K-dependent manner J. Leukoc. Biol., May 1, 2007; 81(5): 1276 - 1286. [Abstract] [Full Text] [PDF] S.-M. Chung, O.-N. Bae, K.-M. Lim, J.-Y. Noh, M.-Y. Lee, Y.-S. Jung, and J.-H. Chung Lysophosphatidic Acid Induces Thrombogenic Activity Through Phosphatidylserine Exposure and Procoagulant Microvesicle Generation in Human Erythrocytes Arterioscler Thromb Vasc Biol, February 1, 2007; 27(2): 414 - 421. [Abstract] [Full Text] [PDF] M. Rahaman, R. W. Costello, K. E. Belmonte, S. S. Gendy, and M.-T. Walsh Neutrophil Sphingosine 1-Phosphate and Lysophosphatidic Acid Receptors in Pneumonia Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 233 - 241. [Abstract] [Full Text] [PDF] D. A. Lin and J. A. Boyce IL-4 Regulates MEK Expression Required for Lysophosphatidic Acid-Mediated Chemokine Generation by Human Mast Cells J. Immunol., October 15, 2005; 175(8): 5430 - 5438. [Abstract] [Full Text] [PDF]

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