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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1996-2003. Prepublished online as a Blood First Edition Paper on October 27, 2005; DOI 10.1182/blood-2005-07-2926. This Article Full Text (PDF) Erratum (v107,p2612) All Versions of this Article: 2005-07-2926v1 107/5/1996    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 Munitz, A. Articles by Levi-Schaffer, F. Search for Related Content PubMed PubMed Citation Articles by Munitz, A. Articles by Levi-Schaffer, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 26, 2005 Accepted October 17, 2005 The inhibitory receptor IRp60 (CD300a) suppresses the effects of IL-5, GM-CSF and eotaxin on human peripheral blood eosinophils Ariel Munitz, Ido Bachelet, Ron Eliashar, Alessandro Moretta, Lorenzo Moretta, and Francesca Levi-Schaffer* Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel Department of Otolaryngology-Head and Neck Surgery, Hebrew University School of Medicine, Hadassah Medical Center, Jerusalem, Israel Dipartimento di Medicina Sperimentale, Universita degli Studi di Genova, Genova, Italy Dipartimento di Medicina Sperimentale, Universita degli Studi di Genova, Genova, Italy; Istituto Gaslini, Genova, Italy Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; The David R. Bloom Center for Pharmacology, The School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Israel * Corresponding author; email: fls{at}cc.huji.ac.il. Allergic, inflammatory and immune responses carried out by eosinophils are regulated by the cross-talk between activatory and inhibitory signals. While much data has been obtained on activatory signals, inhibitory receptors on these cells have received scant attention. Therefore, we screened the surface of human peripheral blood eosinophils for inhibitory receptors using mAbs previously generated to recognize receptors on human natural killer cells. Eosinophils from all of the donors examined expressed the inhibitory receptors IRp60, LIR3/ILT5, FcRIIB and p75/AIRM but not LIR1/ILT2, p58.1, p58.2, p70 or NKG2A/CD94 (n=15). Interestingly, 25% of the donors expressed p140. IRp60 cross-linking inhibited eotaxin-dependent transmigration of eosinophils in a calcium-independent fashion. In addition, cross-linking of IRp60 on the eosinophils in the presence of IL-5/GM-CSF inhibited the anti-apoptotic effect of these cytokines and blocked the release of TNF-, IL-1, IFN-IL-4 and 3T3 fibroblast proliferation. Cross-linking of IRp60 inhibited IL-5-mediated JAK2 phosphorylation as well as eotaxin- and IL-5/GM-CSF-mediated ERK1/2 and p38 phosphorylation. Furthermore, upon cross-linking, IRp60 underwent tyrosine phosphorylation and recruited SHP-1 but not SHP-2. These findings demonstrate a novel pathway for suppressing the activity of human eosinophils thus indicating IRp60 as a future potential target for the treatment of allergic and eosinophil-associated diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Ju, M. Zenke, D. N. J. Hart, and G. J. Clark CD300a/c regulate type I interferon and TNF-{alpha} secretion by human plasmacytoid dendritic cells stimulated with TLR7 and TLR9 ligands Blood, August 15, 2008; 112(4): 1184 - 1194. [Abstract] [Full Text] [PDF] L. Mahajan, T. Madan, N. Kamal, V. K. Singh, R. B. Sim, S. D. Telang, C. N. Ramchand, P. Waters, U. Kishore, and P. U. Sarma Recombinant surfactant protein-D selectively increases apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages Int. Immunol., August 1, 2008; 20(8): 993 - 1007. [Abstract] [Full Text] [PDF] A. Munitz, M. L. McBride, J. S. Bernstein, and M. E. Rothenberg A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils Blood, June 15, 2008; 111(12): 5694 - 5703. [Abstract] [Full Text] [PDF] I. Bachelet, A. Munitz, B. Berent-Maoz, D. Mankuta, and F. Levi-Schaffer Suppression of Normal and Malignant Kit Signaling by a Bispecific Antibody Linking Kit with CD300a J. 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