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.

CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation

“…Indeed, phytohemagglutinin, phorbol myristate acetate, IL-4, interferons, and Epstein-Barr virus infection all upregulate CD48 expression on various hematopoietic cells (16,38). Relevant to this study, we have established that the expression of CD48 on both murine and human eosinophils is upregulated specifically by IL-3 (39). Thus, CD48 is upregulated at the singlecell level by at least two mediators that are expressed in the asthmatic milieu: IL-3 and IL-4.…”

“…Although CD48 has not been studied on these cells in the context of allergic reactions, it may participate in mast cell functions in allergy as well. Moreover, we have shown that CD48 is an activation receptor on human eosinophils and triggers the release of eosinophil peroxidase and eosinophil-derived neurotoxin (39). Consequently, by blocking CD48 we may inhibit lymphocyte, eosinophil, and mast cell activation and cross-talk.…”

2B4 (CD244) is Involved in Eosinophil Adhesion and Chemotaxis, and its Surface Expression is Increased in Allergic Rhinitis after Challenge

“…In humans, 28 4 is expressed in several haemopoietic cells including NK cells, T lymphocytes especially CD8+ T cells as well as subsets of basophils, monocytes and eosinophils (6,(8)(9)(10)(11)(12). Recently, reports have demonstrated a role for C02 in eosinophilic inflammation in experimental asthma and from atopic asthmatics (13)(14)(15). Nonetheless, little is known about the role of these novel molecules in eosinophil recruitment and the pathophysiology ofAR.…”

CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

“…CD48 has recently been linked to eosinophil biology in the context of experimental asthma [8] and allergic airway inflammation [9]. Ligation of CD48 resulted in eosinophil degranulation.…”