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CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils¹

Ariel Munitz^*, Ido Bachelet^*, Ron Eliashar, Marat Khodoun, Fred D. Finkelman, Marc E. Rothenberg and Francesca Levi-Schaffer^2,*,¶

^* Department of Pharmacology, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel; Department of Otolaryngology-Head and Neck Surgery, The Hebrew University School of Medicine, Hadassah Medical Center, Jerusalem, Israel; Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267; Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267; and ^¶ David R. Bloom Center for Pharmacology, The Hebrew University of Jerusalem, Jerusalem, Israel

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.

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