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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2410-2417. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2004-02-0631. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0631v1 104/8/2410    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 Hundley, T. R. Articles by Beaven, M. A. Search for Related Content PubMed PubMed Citation Articles by Hundley, T. R. Articles by Beaven, M. A. Related Collections Signal Transduction Gene Expression Hematopoiesis and Stem Cells Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Kit and FcRI mediate unique and convergent signals for release of inflammatory mediators from human mast cells Thomas R. Hundley, Alasdair M. Gilfillan, Christine Tkaczyk, Marcus V. Andrade, Dean D. Metcalfe, and Michael A. Beaven From the Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. In human mast cells, derived from CD34+ peripheral blood cells, we observed that Kit ligand (KL) failed to induce degranulation but acted in synergy with antigen to markedly enhance degranulation, levels of cytokine gene transcripts, and production of cytokines. Further examination revealed that antigen and KL activated common and unique signaling pathways to account for these varied responses. KL, unlike antigen, failed to activate protein kinase C but activated phospholipase C and calcium mobilization and augmented these signals as well as degranulation when added together with antigen. Both KL and antigen induced signals that are associated with cytokine production, namely phosphorylation of the mitogen-activated protein kinases, phosphatidylinositol 3–kinase–dependent phosphorylation of protein kinase B (also known as Akt), and phosphorylation of nuclear factor B (NFB). However, only KL stimulated phosphorylation of signal transducer and activator of transcription 5 (STAT5) and STAT6, whereas antigen weakly stimulated the protein kinase C–dependent induction and phosphorylation of c-Jun and associated activating protein-1 (AP-1) components, an action that was markedly potentiated by costimulation with KL. Interestingly, most signals were down-regulated on continuous exposure to KL but were reactivated along with cytokine gene transcription on addition of antigen. The findings, in total, indicated that a combination of FcRI and Kit-mediated signals and transcriptional processes were required for optimal physiologic responses of human mast cells to antigen. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-S. Kim, H. S. Kuehn, D. D. Metcalfe, and A. M. Gilfillan Activation and Function of the mTORC1 Pathway in Mast Cells J. Immunol., April 1, 2008; 180(7): 4586 - 4595. [Abstract] [Full Text] [PDF] B. M. Jensen, M. A. Beaven, S. Iwaki, D. D. Metcalfe, and A. M. Gilfillan Concurrent Inhibition of Kit- and Fc{epsilon}RI-Mediated Signaling: Coordinated Suppression of Mast Cell Activation J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 128 - 138. [Abstract] [Full Text] [PDF] C. Akin, L. M. Scott, C. N. Kocabas, N. Kushnir-Sukhov, E. Brittain, P. Noel, and D. D. Metcalfe Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis Blood, October 1, 2007; 110(7): 2331 - 2333. [Abstract] [Full Text] [PDF] B. Li, J. Berman, J.-T. Tang, and T.-J. Lin The Early Growth Response Factor-1 Is Involved in Stem Cell Factor (SCF)-induced Interleukin 13 Production by Mast Cells, but Is Dispensable for SCF-dependent Mast Cell Growth J. Biol. Chem., August 3, 2007; 282(31): 22573 - 22581. [Abstract] [Full Text] [PDF] C. M. Deaton, L. Deaton, E. Jose-Cunilleras, T. L. Vincent, A. W. Baird, K. Dacre, and D. J. Marlin Early onset airway obstruction in response to organic dust in the horse J Appl Physiol, March 1, 2007; 102(3): 1071 - 1077. [Abstract] [Full Text] [PDF] P. Mitra, C. A. Oskeritzian, S. G. Payne, M. A. Beaven, S. Milstien, and S. Spiegel Role of ABCC1 in export of sphingosine-1-phosphate from mast cells PNAS, October 31, 2006; 103(44): 16394 - 16399. [Abstract] [Full Text] [PDF] I. Bachelet, A. Munitz, D. Mankutad, and F. Levi-Schaffer Mast Cell Costimulation by CD226/CD112 (DNAM-1/Nectin-2): A NOVEL INTERFACE IN THE ALLERGIC PROCESS J. Biol. Chem., September 15, 2006; 281(37): 27190 - 27196. [Abstract] [Full Text] [PDF] B. O. Barnstein, G. Li, Z. Wang, S. Kennedy, C. Chalfant, H. Nakajima, K. D. Bunting, and J. J. Ryan Stat5 Expression Is Required for IgE-Mediated Mast Cell Function. J. Immunol., September 1, 2006; 177(5): 3421 - 3426. [Abstract] [Full Text] [PDF] Y. Furumoto, S. Brooks, A. Olivera, Y. Takagi, M. Miyagishi, K. Taira, R. Casellas, M. A. Beaven, A. M. Gilfillan, and J. Rivera Cutting Edge: Lentiviral Short Hairpin RNA Silencing of PTEN in Human Mast Cells Reveals Constitutive Signals That Promote Cytokine Secretion and Cell Survival J. Immunol., May 1, 2006; 176(9): 5167 - 5171. [Abstract] [Full Text] [PDF] H. Qiao, M. V. Andrade, F. A. Lisboa, K. Morgan, and M. A. Beaven Fc{epsilon}R1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells Blood, January 15, 2006; 107(2): 610 - 618. [Abstract] [Full Text] [PDF] T. R. Hundley and B. Rigas Nitric Oxide-Donating Aspirin Inhibits Colon Cancer Cell Growth via Mitogen-Activated Protein Kinase Activation J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 25 - 34. [Abstract] [Full Text] [PDF] S. Iwaki, C. Tkaczyk, A. B. Satterthwaite, K. Halcomb, M. A. Beaven, D. D. Metcalfe, and A. M. Gilfillan Btk Plays a Crucial Role in the Amplification of Fc{epsilon}RI-mediated Mast Cell Activation by Kit J. Biol. Chem., December 2, 2005; 280(48): 40261 - 40270. [Abstract] [Full Text] [PDF]

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