Comparative evaluation of apoptosis induced by Shiga toxin 1 and/or lipopolysaccharides in human monocytic and macrophage-like cells. Academic Article uri icon


  • The enteric pathogens Shigella dysenteriae serotype 1 and Shiga toxin-producing Escherichia coli share the property of expressing the structurally and functionally related cytotoxins that comprise the Shiga toxin (Stx) family. Stx-producing bacteria are causative agents of bloody diarrheal diseases that may progress to life threatening complications involving the destruction of blood vessels in the kidneys and the central nervous system (CNS). The precise mechanisms of toxin transport across the gut epithelial barrier, and the role of innate immunity in the development of systemic complications, remain to be fully characterized. Earlier studies suggested that Stxs and lipopolysaccharides (LPS) induce the expression of proinflammatory cytokines from differentiated (macrophage-like) THP-1 cells. These cytokines may exacerbate vascular damage by up-regulating the expression of toxin receptors on endothelial cells. Purified Stxs have also been shown to induce apoptosis of epithelial and endothelial cells in vitro, but a comparative evaluation of Stx-induced apoptosis of monocytes and macrophages has not been reported. We used FACS, TUNEL, and DNA laddering analyses to show that Shiga toxin-1 (Stx1) and LPS induce apoptosis in undifferentiated and differentiated THP-1 cells, although the kinetics and extent of apoptosis induction differ between monocytic and macrophage-like cells. Stx1-induced apoptosis is A-subunit-dependent. Stx1 and LPS trigger DNA fragmentation and caspase-3 activation, as evidenced by the cleavage of poly(ADP-ribose) polymerase (PARP). Induction of apoptosis in response to Stx1 and/or LPS treatment occurs without the widespread transcriptional activation of apoptosis-related genes. Finally, we present a model of the role of macrophages and monocytes in the pathogenesis of disease caused by Stxs.

published proceedings

  • Microb Pathog

author list (cited authors)

  • Harrison, L. M., Cherla, R. P., van den Hoogen, C., van Haaften, W., Lee, S., & Tesh, V. L.

citation count

  • 38

complete list of authors

  • Harrison, Lisa M||Cherla, Rama P||van den Hoogen, Christel||van Haaften, Wilhelmina CE||Lee, Sang-Yun||Tesh, Vernon L

publication date

  • February 2005