title: 2B4 (CD244) is expressed and functional on human eosinophils.
abstract: Eosinophils are present in parasitic, allergic, various immunological, and malignant disorders as well as in a variety of idiopathic hypereosinophilic syndromes. However, their exact role in some of these conditions remains elusive. They can be activated both in vivo and in vitro by various agonists, such as Igs, lipid mediators, and cytokines. By phenotyping the surface of the eosinophils, it may be possible to better define their function(s) in different pathophysiological settings. In the present work we screened eosinophils with a panel of Abs recognizing CD2 subfamily receptors usually present on a number of hemopoietic cells. We have demonstrated that human peripheral blood eosinophils, but not basophils or neutrophils, express NTB-A. In addition eosinophils express 2B4, CD84, CD58, and CD48, but not signaling lymphocytic activation molecule or CD2, on their surface (FACS). Cross-linking of 2B4 on eosinophils elicited a significant release of eosinophil peroxidase (30 min), IFN-gamma, and IL-4 (18 h). Moreover, activation of eosinophils via 2B4 induced eosinophil-mediated cytotoxicity toward two malignant cell lines, i.e., mouse mastocytoma P815 and EBV-infected 721.221 B cell lines. Cross-linking of 2B4 on the surface of eosinophils or pervenadate treatment elicited ERK and tyrosine phosphorylation, respectively. Furthermore, we showed that eosinophils express slam-associated protein. The demonstration that human eosinophils express a functional 2B4 receptor indicates a broader role for these cells in health and disease.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Munitz
authors.forename: Ido
authors.initials: I
authors.lastname: Bachelet
authors.forename: Shira
authors.initials: S
authors.lastname: Fraenkel
authors.forename: Gil
authors.initials: G
authors.lastname: Katz
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
authors.forename: Hans-Uwe
authors.initials: HU
authors.lastname: Simon
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D000071178:CD48 Antigen; D018968:CD58 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D047209:Eosinophil Peroxidase / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; D018968:CD58 Antigens; C498970:CD84 protein, human; C000604066:Cd48 protein, mouse; D006023:Glycoproteins; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C000604060:SLAMF6 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; C000604063:Slamf6 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D015847:Interleukin-4; D007371:Interferon-gamma; D047209:Eosinophil Peroxidase