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Blood, 1 January 2007, Vol. 109, No. 1, pp. 203-211. Prepublished online as a Blood First Edition Paper on September 25, 2006September 21, 2006; DOI 10.1182/blood-2006-06-025882. This Article Full Text (PDF) All Versions of this Article: blood-2006-06-025882v1 blood-2006-06-025882v2 109/1/203    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 Kanamaru, Y. Articles by Monteiro, R. C Search for Related Content PubMed PubMed Citation Articles by Kanamaru, Y. Articles by Monteiro, R. C Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 2, 2006 Accepted August 12, 2006 IgA Fc receptor I signals apoptosis through the FcRITAM and affects tumor growth Yutaka Kanamaru, Houda Tamouza, Severine Pfirsch, Delphine Elmehdi, Claudine Guerin-Marchand, Marina Pretolani, Ulrich Blank, and Renato C Monteiro* Institut National de la Sante et de la Recherche Medicale, U699, Bichat Medical School, Paris, FR Institut National de la Sante et de la Recherche Medicale, U700, Bichat Medical School, Paris, FR * Corresponding author; email: monteiro{at}bichat.inserm.fr. The IgA Fc receptor (FcRI) has dual pro- and anti-inflammatory functions that are transmitted through the immunoreceptor tyrosine-based activation motifs (ITAM) of the associated FcR subunit. While the involvement of FcRI in inflammation is well documented, little is known of its anti-inflammatory mechanisms. Here we show that monomeric targeting of FcRI by anti-FcRI Fab or serum IgA triggers apoptosis in human monocytes, monocytic cell lines and FcRI+ transfectants. However, the physiological ligand IgA induced apoptosis only when cells were cultured in low serum conditions, indicating differences with induction of anti-inflammatory signaling. Apoptosis signaling required the FcR ITAM, as cells transfected with FcRI or with a chimeric FcRI-FcR responded to death-activating signals, while cells expressing a mutated FcR209L unable to associate with FcR, or an ITAM-mutated chimeric FcRI-FcR, did not respond. FcRI-mediated apoptosis signals were blocked by treatment with the pan-caspase inhibitor zVADfmk, involved proteolysis of procaspase-3, and correlated negatively with SHP-1 concentration. Anti-FcRI Fab treatment of nude mice injected subcutaneously with FcRI+ mast cell transfectants prevented tumor development and halted the growth of established tumors. These findings demonstrate that, upon monomeric targeting, FcRI functions as an FcR ITAM-dependent apoptotic module that may be fundamental for controlling inflammation and tumor growth. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: FcRI: a case of multiple personality disorder? Marjolein van Egmond Blood 2007 109: 1-2. [Full Text] [PDF] This article has been cited by other articles: Y. Kanamaru, S. Pfirsch, M. Aloulou, F. Vrtovsnik, M. Essig, C. Loirat, G. Deschenes, C. Guerin-Marchand, U. Blank, and R. C. Monteiro Inhibitory ITAM Signaling by Fc{alpha}RI-FcR{gamma} Chain Controls Multiple Activating Responses and Prevents Renal Inflammation J. Immunol., February 15, 2008; 180(4): 2669 - 2678. [Abstract] [Full Text] [PDF]

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