Damage to Schistosomula of Schistosoma Mansoni Induced Directly by Eosinophil Major Basic Protein

Abstract

Major basic protein (MBP) from both human and guinea pig eosinophils has been found to damage schistosomula of Schistosoma mansoni at concentrations as low as 2 × 10-5 M. This damage can be detected both by light microscopy and by measurement of release of 51Cr from labeled larvae. Damage is attributable in part to the basic properties of the molecule, since some other cations of comparable molecular weight, such as protamine and polyarginine, have comparable effects at equimolar concentrations. Other cations, however, fail to mediate damage, indicating that simply the possession of a positive charge is a necessary but insufficient prerequisite. The action of MBP is not selective, since mammalian target cells can also be damaged. Damage induced by MBP is associated with uptake of the material onto the parasite's surface, and both uptake and damage can be blocked by heparin. In addition, it has been found that MBP is released during the antibody-dependent reaction between human eosinophils and schistosomula, and can be detected both on the surface of the organism and free in small quantities in the supernatant. Damage mediated directly by eosinophils is not inhibitable by heparin, suggesting that the effect of eosinophils is attributable to the local release of high concentrations of MBP into a sequestered site adjacent to the parasite surface, rather than to a generalized release into the supernatant. These findings suggest that release of MBP may represent a major mechanism of eosinophil-mediated damage to schistosomula and, since MBP is uniquely associated in high quantities with the eosinophil, these results provide a partial explanation for the selective action of eosinophils on antibody-coated schistosomula.