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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.
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IMMUNOBIOLOGY
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
From the Department of Pharmacology, School of Pharmacy, Faculty of Medicine, the Hebrew University of Jerusalem, Israel; Department of Otolaryngology-Head and Neck Surgery, the Hebrew University School of Medicine, Hadassah Medical Center, Jerusalem, Israel; Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genoa, Italy; Istituto Gaslini, Genoa, Italy; and the David R. Bloom Center for Pharmacology, the School of Pharmacy, Faculty of Medicine, the Hebrew University of Jerusalem, Israel.
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 monoclonal antibodies (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, Fc RIIB, 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 antiapoptotic 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.
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