title: CD48 is an allergen and IL-3-induced activation molecule on eosinophils.
abstract: Eosinophils are involved in a variety of allergic, parasitic, malignant, and idiopathic disorders by releasing a variety of factors including specific granule proteins, lipid mediators, and proinflammatory and immunoregulatory cytokines and chemokines. In addition, they interact with various cell types in the inflamed tissue. Yet, the mechanism of eosinophil activation is still poorly understood. Recently, we described the expression and function of the CD2-subfamily of receptors and especially 2B4 on human eosinophils. In this study we focus on CD48, the high-affinity ligand of 2B4. CD48 is a GPI-anchored protein involved in cellular activation, costimulation, and adhesion, but has not been studied on eosinophils. We demonstrate that human eosinophils from atopic asthmatics display enhanced levels of CD48 expression and that IL-3 up-regulates CD48 expression. Furthermore, cross-linking CD48 on human eosinophils triggers release of eosinophil granule proteins. Assessment of CD48 expression in a murine model of experimental asthma revealed that CD48 is induced by allergen challenge and partially regulated by IL-3. Additionally, anti-IL-3 reduces CD48 expression and the degree of airway inflammation. Thus, CD48 is an IL-3-induced activating receptor on eosinophils, likely involved in promoting allergic inflammation.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The 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: Ron
authors.initials: R
authors.lastname: Eliashar
authors.forename: Marat
authors.initials: M
authors.lastname: Khodoun
authors.forename: Fred D
authors.initials: FD
authors.lastname: Finkelman
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D000071178:CD48 Antigen; D002478:Cells, Cultured; D004195:Disease Models, Animal; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009298:Nasal Polyps / Q000276:immunology / Q000473:pathology; D010538:Peritonitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000485:Allergens; D015703:Antigens, CD; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C000604066:Cd48 protein, mouse; D007377:Interleukin-3; D047209:Eosinophil Peroxidase