Molecular mechanisms of cytotoxicity mediated by Entamoeba histolytica: Characterization of a pore‐forming protein (PFP)

Entamoeba histolytica is the human pathogen responsible for amebiasis. This infection is characterized by an invasive enteric illness that may spread to multiple organs. The parasite E histolytica may now be cultivated in vitro, with Diamond's axenic medium [1]. In culture, this protozoan remains cytolytic to a variety of cell types, including neutrophils and macrophages (reviewed in [2]). The mechanism(s) involved in the expression of this potent cytolysis remain(s) unclear. Previous studies from several laboratories have suggested that the cell killing mediated by amoeba is dependent on intimate contact of amoeba with the target cell membrane [3–9]. Following contact, the amoeba readily ingests the target cell (Fig. 1A). However, more recent cinemicroscopic and kinetic studies [8,9] (see also Fig. 1B) indicate that the cytolysis mediated by amoeba may occur prior to phagocytosis, raising the possibility of an extracellular cytolytic event triggered by surface contact. Previous work from this laboratory has described the properties of a highly enriched plasma membrane fraction and surface polypeptides from axenically grown E histolytica [10,11]. Studies from this laboratory on its extensive vacuolar apparatus and its role in pinocytosis and intracellular acidification have also been published [12,13]. Here, we review some recent evidence for the isolation and characterization of a pore‐forming protein (PFP) extracted from this protozoan, which may be closely related to the killing of target cells mediated by pore‐forming proteins of the immune system (the complement cascade as well as proteins extracted from granules of different immune cells [Young et al, in preparation]), which may thereby suggest a very similar and general mechanism of cell‐mediated cytotoxicity.