Mouse eosinophil associated ribonucleases: Mechanism of cytotoxic, antibacterial and antiparasitic activities

Ribonuclease A family is a group of proteins having similar structures and catalytic mechanism but different functions. Human eosinophil granules contain two ribonucleases belonging to the RNase A family, eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN). In mouse, 15 orthologs of EDN and ECP, called mouse eosinophil associated ribonucleases (mEARs) have been reported which are expressed under different pathophysiological conditions. In this study, we have characterized mEAR2, mEAR5, mEAR7 and mEAR11, and compared them with ECP for their catalytic, cytotoxic, antibacterial and antiparasitic activities. All four mEARs had cytotoxic, antibacterial and antiparasitic activities. Generally, mEAR5 and mEAR2 were more cytotoxic than mEAR7, mEAR11 and ECP. The antimicrobial activities of mEAR7 and mEAR5 were higher than those of mEAR11 and mEAR2. The cytotoxic activity appeared to be associated with the basicity and RNase activity of mEARs, whereas no such correlation was observed for antimicrobial activities. The differential selective expression of mEARs under various pathophysiological conditions may be associated with the different biological activities of various mEARs.