Structural Bases of the Cytolytic Mechanisms of Entamoeba histolytica¹

Abstract

The cellular bases of the powerful cytolytic activity of the human protozoan parasite Entamoeba histolytica were explored by studying the effect of the virulent strain HM1:IMSS on epithelial monolayers of MDCK cells using a combination of time-lapse microcinematography and transmission and scanning electron microscopy. Early alterations of the epithelial cell membranes were detected by measuring changes in the transepithelial electrical resistance of MDCK monolayers mounted in Ussing chambers. The aggressive mechanism of E. histolytica trophozoites was found to be a complex, multifactorial phenomenon that included hit-and-run damage to the plasma membrane of effector cells mediated through contact, phagocytosis of lysed or apparently intact, but detached, MDCK cells, and intracellular degradation of ingested cells. Following contact with amebas, the epithelial monolayers showed a pronounced lowering of transepithelial resistance, opening of tight junctions, distortion of microvilli, surface blebbing, and the presence of minute focal discontinuities in the plasma membrane. There was no evidence of amebic exocytosis, membrane fusion, or junction formation between the parasite and host plasma membranes. Although modifications in the epithelial cell membranes usually preceded lysis, the cytolytic activity of the parasite did not exclusively involve damage to the plasma membrane of the cultured host cells but also was mediated by avid phagocytosis, the displacement and separation of neighboring cells by means of pseudopodial activity, and the "pinching-off" of the peripheral cytoplasm of epithelial cells.

Inhibition of chemiluminescent response of olive flounder Paralichthys olivaceus phagocytes by the scuticociliate parasite Uronema marinum

“…Cross & Matthews (1993) reported that carp leukocytes which come into close contact with Ichthyophthirius multifiliis trophozoites are generally degraded, presumably due to lytic enzymes and/or metabolites released by the parasite. Cell infiltration around invading Entamoeba histolytica also leads to rapid lysis of inflammatory cells followed by tissue necrosis (Martínez-Palomo et al 1985, Shibayama et al 1997.…”

Pathogenesis of Intestinal Amebiasis: From Molecules to Disease

“…3). In vitro, time-lapse microcinematography has shown that the aggressive mechanism of E. histolytica is a complex multifactorial phenomenon that includes adhesion, a contact-dependent "hit-and-run" damage to the plasma membrane of effector cells, phagocytosis, and intracellular degradation of ingested cells (86). The adhesion and cytolytic events have been related to three types of molecules: lectins, amebapores, and proteases.…”

Ups and Downs of Mucosal Cellular Immunity against Protozoan Parasites

“…Tight junction complexes are linked to the actin cytoskeleton (60). Selective disturbance of tight junction complexes by trophozoites from E. histolytica results in the rapid decrease of the transepithelial electrical resistance caused by an increase in paracellular permeability (51,54,61).…”