Selectin and Lewisx are required as co-receptors in antibody-dependent cell-mediated cytotoxicity of human eosinophils toSchistosoma mansoni schistosomula

Abstract

Killing of Schistosoma mansoni larvae by human eosinophils via antibody-dependent cell-mediated cytotoxicity (ADCC) mechanisms requires adherence between effector cells and parasite targets. The role of adhesion molecules in this mechanism was investigated using blocking monoclonal antibodies (mAb) and soluble ligands. We show that, along with the Mac-1 alpha chain, interactions between selectins and LewisX-related structures, both expressed by eosinophils and parasite targets, play a critical part in the antibody-dependent cytotoxic function of eosinophils. To further elucidate the interactions between adhesion molecules and eosinophil Fc receptors, ADCC was performed with IgG1 or IgA mAb. We found that mAb directed against Mac-1 alpha chain or against LewisX could significantly inhibit the IgG1-, but not IgA cytotoxicity. This result might be explained, at least in part, by the inhibitory effect of these mAb on the release by eosinophils of eosinophil cationic protein, one of the major mediators involved in target killing. Taken together, these results suggest novel interactions between Fc receptors and selectins and LewisX-related structures which might act as co-receptors for eosinophil-mediated cytotoxicity.