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^1-3. Cytolysis may involve a secretory phenomenon whereby granule proteins are released at the site of contact between eosinophil and target cells^1-4. Several basic proteins have been isolated from eosinophil granules, including the major basic protein^5-7, eosinophil cationic protein^8,9, eosinophil protein-X¹⁰ and eosinophil peroxidase¹¹. One of the major granule proteins of human eosinophils is the eosinophil cationic protein (ECP)^3,8,9 which has been shown to damage schistosomula of Schistosoma mansoni at concentrations as low as 10^-7 M (Ref. 12). 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^13-20 may represent a general and effective mechanism of target cell killing.