SEARCH:   Advanced

Blood, 15 July 2007, Vol. 110, No. 2, pp. 561-567. Prepublished online as a Blood First Edition Paper on March 16, 2007; DOI 10.1182/blood-2006-10-052258. This Article Full Text (PDF) All Versions of this Article: blood-2006-10-052258v1 110/2/561    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 Kikawada, E. Articles by Arm, J. P Search for Related Content PubMed PubMed Citation Articles by Kikawada, E. Articles by Arm, J. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 17, 2006 Accepted February 6, 2007 Group V secretory PLA2 regulates TLR2-dependent eicosanoid generation in mouse mast cells through amplification of ERK and cPLA2 activation Eriya Kikawada, Joseph V Bonventre, and Jonathan P Arm* Department of Medicine, Harvard Medical School, Boston, MA, United States Renal Division, Brigham and Women's Hospital, Boston, MA, United States Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, United States * Corresponding author; email: jarm{at}rics.bwh.harvard.edu. Mast cells may be activated through Toll-like receptors (TLRs) for the dose- and time-dependent release of eicosanoids. However, the signaling mechanisms of TLR-dependent rapid eicosanoid generation are not known. We previously reported a role for group V secretory phospholipase A2 (PLA2) in regulating phagocytosis of zymosan and the ensuing eicosanoid generation in mouse resident peritoneal macrophages, suggesting a role for the enzyme in innate immunity. In the present study, we have used gene knockout mice to define an essential role for MyD88 and cytosolic PLA2 in TLR2-dependent eicosanoid generation. Furthermore, in mast cells lacking group V secretory PLA2, the time course of phosphorylation of ERK1/2 and of cPLA2 were markedly truncated leading to attenuation of eicosanoid generation in response to stimulation through TLR2, but not through c-kit or FcRI. These findings provide the first dissection of the mechanisms of TLR-dependent rapid eicosanoid generation, which is MyD88-dependent, requires cPLA2, and is amplified by group V sPLA2 through its regulation of the sequential phosphorylation and activation of ERK1/2 and cPLA2. They support the suggestion that group V sPLA2 regulates innate immune responses. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. C. Lindner, U. Kohl, T. J. Maier, D. Steinhilber, and B. L. Sorg TLR2 ligands augment cPLA2{alpha} activity and lead to enhanced leukotriene release in human monocytes J. Leukoc. Biol., August 1, 2009; 86(2): 389 - 399. [Abstract] [Full Text] [PDF] V. Ruiperez, A. M. Astudillo, M. A. Balboa, and J. Balsinde Coordinate Regulation of TLR-Mediated Arachidonic Acid Mobilization in Macrophages by Group IVA and Group V Phospholipase A2s J. Immunol., March 15, 2009; 182(6): 3877 - 3883. [Abstract] [Full Text] [PDF] I. Valera, N. Fernandez, A. G. Trinidad, S. Alonso, G. D. Brown, A. Alonso, and M. S. Crespo Costimulation of Dectin-1 and DC-SIGN Triggers the Arachidonic Acid Cascade in Human Monocyte-Derived Dendritic Cells J. Immunol., April 15, 2008; 180(8): 5727 - 5736. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020