HUMAN MONOCYTE-DERIVED MACROPHAGES INFECTED WITH VIRULENT SHIGELLA-FLEXNERI IN-VITRO UNDERGO A RAPID CYTOLYTIC EVENT SIMILAR TO ONCOSIS BUTNOT APOPTOSIS

Infection of human monocyte-derived macrophages in vitro with virulent Shigella flexneri resulted in cell death which involved rupture of th e plasma membrane, cell swelling, disintegration of ultrastructure, an d generalized karyolysis, These features bore resemblance to oncosis a nd are in striking contrast to previously described observations of mo use macrophages, where a similar infection by virulent Shigella result ed in cell death by apoptosis, Cell death by oncosis in human macropha ges was confirmed by lactate dehydrogenase release, light microscopy, electron microscopy, terminal deoxynucleotidyltransferase end labeling of DNA ends, DNA fragmentation assays, and fluorescence-activated cel l sorter analysis of propidium-labeled nuclei. Thus, the phenomena of cell death induced by virulent Shigella in human and mouse macrophages reflect different biochemical pathways. Interleukin-1 beta (IL-1 beta ) was released in culture supernatants of human macrophages infected w ith virulent bacteria, Inhibition with IL-lp-converting enzyme inhibit ors indicated, however, that this release occurred as a passive event of cell lysis, The patterns of intracellular survival of Shigella stra ins within human and mouse macrophages reflect differences that exist not only between Shigella serotypes but also between the two different macrophage cell types.