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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4193-4200. Prepublished online as a Blood First Edition Paper on January 4, 2008; DOI 10.1182/blood-2007-09-115451. This Article Full Text (PDF) All Versions of this Article: blood-2007-09-115451v1 111/8/4193    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 Oskeritzian, C. A Articles by Spiegel, S. Search for Related Content PubMed PubMed Citation Articles by Oskeritzian, C. A Articles by Spiegel, S. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 28, 2007 Accepted December 20, 2007 Distinct roles of sphingosine kinases 1 and 2 in human mast cell functions Carole A Oskeritzian, Sergio E Alvarez, Nitai C Hait, Megan M Price, Sheldon Milstien, and Sarah Spiegel* Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, United States National Institute of Mental Health, NIH, Bethesda, MD, United States * Corresponding author; email: sspiegel{at}vcu.edu. Sphingosine-1-phosphate (S1P) is now emerging as a potent lipid mediator produced by mast cells that contributes to inflammatory and allergic responses. In contrast to its weak effect on degranulation of murine mast cells, S1P potently induced degranulation of the human LAD2 mast cell line and cord blood-derived human mast cells (hMC). S1P also stimulated production and secretion of the cytokines, TNF- and IL-6, and markedly enhanced secretion of the chemokine, CCL2/MCP-1, important modulators of inflammation. S1P is produced in mast cells by the two sphingosine kinases, SphK1 and SphK2. SphK1 but not SphK2 plays a critical role in IgE/Ag-induced degranulation, migration toward antigen, and CCL2 secretion from hMC, as determined by specifically downregulating their expression. However, both isoenzymes were required for efficient TNF- secretion. Taken together, our data suggest that differential formation of S1P by SphK1 and SphK2 has distinct and important actions in hMC. 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] P. N. Pushparaj, J. Manikandan, H. K. Tay, S. C. H'ng, S. D. Kumar, J. Pfeilschifter, A. Huwiler, and A. J. Melendez Sphingosine Kinase1 Is Pivotal for Fc{epsilon}RI-Mediated Mast Cell Signaling and Functional Responses In Vitro and In Vivo J. Immunol., July 1, 2009; 183(1): 221 - 227. [Abstract] [Full Text] [PDF] M. Maceyka, S. Milstien, and S. Spiegel Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling J. Lipid Res., April 1, 2009; 50(Supplement): S272 - S276. [Abstract] [Full Text] [PDF] G. Bansal, J. A. DiVietro, H. S. Kuehn, S. Rao, K. H. Nocka, A. M. Gilfillan, and K. M. Druey RGS13 Controls G Protein-Coupled Receptor-Evoked Responses of Human Mast Cells J. Immunol., December 1, 2008; 181(11): 7882 - 7890. [Abstract] [Full Text] [PDF] S. Uhlig and E. Gulbins Sphingolipids in the Lungs Am. J. Respir. Crit. Care Med., December 1, 2008; 178(11): 1100 - 1114. [Abstract] [Full Text] [PDF]

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