Involvement of complement and fibronectin in eosinophil-mediated damage toNippostrongylus brasiliensislarvae

By using IL-5 transgenic mice, it has been shown that eosinophils might play a key role in elimination of larval stages of nematode infections. The present study was carried out to clarify molecular mechanisms involved in the eosinophil-mediated killing of Nippostrongylus brasiliensis larvae. The larvicidal activity was observed in the presence of normal serum in vitro. Electron microscopic observations revealed firm attachment of eosinophils to the cuticular surface of larvae, which was damaged by electron-dense materials released from eosinophils. The larvicidal activity was abrogated by heat- or zymosan-treatment of the serum, whereas depletion of IgG or IgM from the serum did not interfere with eosinophil adhesion and killing. Moreover, pretreatment of eosinophils with monoclonal antibodies against CD11b or VLA-4 inhibited the eosinophil-mediated killing of larvae. Immunofluorescent staining demonstrated the deposition of C3c and plasma fibronectin on the cuticle of the larvae. These results indicate that interactions between CD11b and VLA-4 and their respective counter-ligands deposited on the cuticle are essential in eosinophil-mediated adhesion and damage to larvae of N. brasiliensis.