IgE‐binding molecules (Mac‐2/ϵBP) expressed by human eosinophils. Implication in IgE‐dependent eosinophil cytotoxicity

Abstract

Macrophage cell‐surface protein 2 (Mac‐2), a galactose specific S‐type lectin identified in inflammatory macrophages, presents a high degree of homology with the rat IgE‐binding protein (ϵBP). In the present study, we show by different experimental approaches that human eosinophils can express Mac‐2/ϵBP. Flow cytometry analysis revealed that a large proportion of eosinophilic patients expressing binding sites for IgE on their eosinophil membrane, were able to bind anti‐Mac‐2 monoclonal antibody (mAb). Northern blot performed with eosinophil RNA hybridized with the human Mac‐2 or ϵBP cDNA probes revealed that eosinophils presented a unique transcript at 1.2 kb. Immunoprecipitation of eosinophil extracts with anti‐Mac‐2 mAb revealed the presence of a molecule of 29 kDa corresponding to Mac‐2 protein, as well as one additional molecule of 15 kDa, absent from control alveolar macrophages. The function of these molecules was investigated in a radiolabeled IgE binding assay. Anti‐Mac‐2 mAb as well as galactose and lactose saccharides significantly inhibited the binding of radiolabeled human myeloma IgE protein to eosinophils. Moreover, the dose‐dependent inhibition by anti‐Mac‐2 mAb of IgE‐dependent eosinophil‐mediated cytotoxicity towards parasite targets indicated the role of these IgE‐binding molecules in the function of human eosinophils. These results suggest that in addition to transmembrane receptors, lectin‐type molecules can participate in the IgE‐dependent effector function of eosinophils.