Selectin and Lewis(X) are required as co-receptors in antibody-dependent cell-mediated cytotoxicity of human eosinophils to Schistosoma mansoni schistosomula

Killing of Schistosoma mansoni larvae by human eosinophils via antibody-dep endent cell-mediated cytotoxicity (ADCC) mechanisms requires adherence betw een 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, intera ctions between selectins and Lewis(x)-related structures, both expressed by eosinophils and parasite targets, play a critical part in the antibody-dep endent cytotoxic function of eosinophils. To further elucidate the interact ions between adhesion molecules and eosinophil Fc receptors, ADCC was perfo rmed with IgG1 or IgA mAb. We found that mAb directed against Mac-1 alpha c hain or against Lewis(x) could significantly inhibit the IgG1-, but not IgA cytotoxicity. This result might be explained, at least in part, by the inh ibitory effect of these mAb on the release by eosinophils of eosinophil cat ionic protein, one of the major mediators involved in target killing. Taken together, these results suggest novel interactions between Fc receptors an d selectins and Lewis(x)-related structures which might act as co-receptors for eosinophil-mediated cytotoxicity.