Dynamics and function of eosinophils’ CD48 molecules in allergic rhinitis and in response to eotaxin stimulation

Abstract

Background : The functional expression of eosinophil's CD48 molecules that act in the form of ligand–receptor pairs with 2B4 (CD244), in allergic rhinitis (AR) and in response to eotaxin stimulation, is studied. Methodology : Nasal allergen provocation, flow cytometry, adhesion assay, confocal microscopy and westren blot were used in the current study. Results : Herein, it is shown that following a single nasal allergen challenge with the house dust mite (HDM), the percentage of peripheral blood eosinophils expressing total CD48 molecules increased in 100% of AR patients ( n =10) sensitized to HDM and lasted up to 24 h, while the surface expression increased in 20% of these patients and lasted for 6 h. After challenge, a significant increase of eosinophil adhesion and intercellular adhesion to collagen type IV coated slides was observed. Eotaxin induced the surface expression of CD48 in eosinophils from normal subjects and AR patients. This was sensitive to genistein, a tyrosine kinase inhibitor. Eotaxin-induced eosinophil adhesion was blocked in a dose-dependent fashion by anti-CD48 Ab. Eosinophil stimulation with functional grade purified C1.7 Ab induced F-actin increase and eosinophil shape changes that were sensitive to genistein. Western blot analysis identified low-molecular-weight tyrosine kinase protein residues phosphorylation by eotaxin and C1.7 Ab. Conclusion: These results identify the CD48–2B4 complex to be involved in eosinophil functional responses, making them novel targets for therapeutic approaches to eosinophilic inflammation of the airway. Keywords: eosinophils; intercellular adhesion; adhesion; allergic rhinitis; CD48; 2B4 Citation: Advances in Cellular and Molecular Otolaryngology 2013, 1 : 22389 - http://dx.doi.org/10.3402/acmo.v1i0.22389