Mechanism of membrane damage mediated by human eosinophil cationic protein

Recent evidence suggests a role for eosinophil granule proteins in contact-dependent antibody-mediated cytotoxicity. Cytolysis may involve a secretory phenomenon whereby granule proteins are released at the site of contact between eosinophil and target cells. Several basic proteins have been isolated from eosinophil granules, including the major basic protein, eosinophil cationic protein, eosinophil protein-X and eosinophil peroxidase. One of the major granule proteins of human eosinophils is the eosinophil cationic protein (ECP) which has been shown to damage schistosomula of Schistosoma mansoni at concentrations as low as 10(-7). Here, we describe the formation of functional channels by purified human ECP. The transmembrane pores formed by ECP are relatively voltage-insensitive and non-ion-selective, suggesting a role for channel formation by ECP in target cell damage mediated by eosinophils. Channel formation by granule proteins of immune effector cells may represent a general and effective mechanism of target cell killing.