Entamoeba histolytica: from Adherence to Enteropathy Jonathan I. Ravdin From the Departments of Medicine and Pharmacology, Divisions of Clinical Pharmacology, Geographic Medicine,

En/amoeba histolytica, a cause of invasive colitis or liver abscess, is responsible for sub-stantial worldwide morbidity and mortality. An understanding of the biochemical basis for the parasite adherence and cytolytic activities and antiamebic host immune response mechanisms are prerequisites for vaccine development. The E. histolyticagalactose (Gal) or N-acetyl-D-galactosamine (GaINAc) inhibitable adherence lectin mediates attachment of trophozoites to colonic mucins or mammalian target cells. Amebic cytolysis of target cells requires GaIlGaINAc-lectin-mediated adherence, parasite phospholipase A activity, and maintenance of an acid pH in amebic intracellular vesicles.Cytolytic activity is stimu-lated by phorbol esters (activators of protein kinase C) and results from an E. histolyt-ica-mediated increase in free Ca " within the target cell. The GallGalNAc adherence lec-tin is a highly conserved antigen that is universally recognized by human immune sera; patients cured of invasive amebiasis possess antigen-specific cell-mediated immunity ef-fective in vitro against E. histolytica trophozoites. Promising vaccines include the puri-fied adherence lectin, for eliciting an intestinal secretion of IgA antibody to lectin, and additional E. histolytica antigens, which elicit cell-mediated amebicidal responses