Towards the immunological control of human protozoal diseases - Cytopathogenicity of Entamoeba histolytica

The lesions induced in man by Entamoeba histolytica are characterized by massive tissue injury in the absence of major local signs of a host immune response. The amoeba damages surrounding cells preferentially by contact-mediated cytolysis. Recently, a presumptive aetiological factor underlying this process has been identified. It is a protein, amoebapore, capable of spontaneous incorporation into host cell membranes. Therein it induces high conductance ion-channels which rapidly collapse the cellular transmembrane potential and lead to a prelytic state. Amoebapore is present within the amoeba in a highly aggregated state in a small, dense particle. It is shed into the medium in a particulate form by a stimulus-mediated process. Release is enhanced by addition of concanavalin A, lipopolysaccharide or the calcium ionophore A23187. Surface-labelling of intact amoeba, followed by fractionation of the homogenate in self-generating Percoll gradients, identified two labelled fractions, the plasma membrane and a particulate fraction sedimenting in the region of intracellular particulate amoebapore. This latter fraction appears to be material in the process of exocytosis. A highly immunogenic surface lipid has been identified and shown to be involved in the rapid surface redistribution of immune complexes, their shedding and endocytosis. The relevance of these findings to the immunoprophylaxis of amoebiasis is discussed.