Induction of apoptosis in normal human renal tubular epithelial cells by Escherichia coli Shiga toxins 1 and 2.

The cytotoxicity of Shiga toxin (Stx) 1 and Stx2 produced by Escherichia coli to human renal cortical epithelial cells (HRCEC) in primary culture was investigated. HRCEC express CD24, the marker of renal distal tubules, as well as globotriaosyl ceramide/CD77, the receptor for Stxs. Binding of Stxs to HRCEC was confirmed by positive staining with specific antibodies to Stxs. Treatment of HRCEC with Stxs induced rapid cell death, which was reversed in the presence of neutralizing antibody specific for Stx. DNA fragmentation was found to be accompanied by Stx-mediated cell death in HRCEC, indicating that apoptosis was part of the process. These data and previous reports indicate that a variety of renal cell types, including tubular epithelial cells as well as glomerular capillary endothelial cells, may be targets for Stx-mediated apoptosis, which could contribute to the pathogenesis of hemolytic-uremic syndrome caused by Stx-producing E. coli infection.

[1]  H. Uchida,et al.  Verotoxins induce apoptosis in human renal tubular epithelium derived cells. , 1998, Kidney international.

[2]  T. Tursz,et al.  Intracellular signaling events in CD77-mediated apoptosis of Burkitt's lymphoma cells. , 1997, Blood.

[3]  D. Milford,et al.  Comparison of ribosome-inactivating proteins in the induction of apoptosis. , 1997, Toxicology letters.

[4]  E. Jaffe,et al.  Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells. , 1997, Blood.

[5]  Z. Ao,et al.  A mitochondrial membrane protein defined by a novel monoclonal antibody is preferentially detected in apoptotic cells. , 1996, Journal of immunology.

[6]  E. Jaffe,et al.  Plasma From Patients With Idiopathic and Human Immunodeficiency Virus- Associated Thrombotic Thrombocytopenic Purpura Induces Apoptosis in Microvascular Endothelial Cells , 1996 .

[7]  M. Ueffing,et al.  Critical involvement of transmembrane tumor necrosis factor-alpha in endothelial programmed cell death mediated by ionizing radiation and bacterial endotoxin. , 1995, Blood.

[8]  D. Milford,et al.  Verocytotoxin-1 induces apoptosis in vero cells. , 1995, The Journal of infection.

[9]  M. Peterson,et al.  Induction of Endothelial Cell Apoptosis by TNFα: Modulation by Inhibitors of Protein Synthesis , 1994 .

[10]  Z. Darżynkiewicz,et al.  A selective procedure for DNA extraction from apoptotic cells applicable for gel electrophoresis and flow cytometry. , 1994, Analytical biochemistry.

[11]  B. Caillou,et al.  Apoptosis induced in Burkitt's lymphoma cells via Gb3/CD77, a glycolipid antigen. , 1993, Cancer research.

[12]  T. Takeda,et al.  Impairment by verotoxin of tubular function contributes to the renal damage seen in haemolytic uraemic syndrome. , 1993, The Journal of infection.

[13]  A. Melton,et al.  Virulence of enterohemorrhagic Escherichia coli O91:H21 clinical isolates in an orally infected mouse model , 1993, Infection and immunity.

[14]  C. Lingwood,et al.  Shiga toxin-associated hemolytic uremic syndrome: interleukin-1 beta enhancement of Shiga toxin cytotoxicity toward human vascular endothelial cells in vitro , 1993, Infection and immunity.

[15]  J. Samuel,et al.  Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice , 1993, Infection and immunity.

[16]  C. Lingwood,et al.  Endothelial heterogeneity in Shiga toxin receptors and responses. , 1993, The Journal of biological chemistry.

[17]  T. Barratt,et al.  Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. , 1992, Kidney international.

[18]  B. Deurs,et al.  Toxin-induced cell lysis: protection by 3-methyladenine and cycloheximide. , 1992, Experimental cell research.

[19]  J. Samuel,et al.  Evaluation of the role of Shiga and Shiga-like toxins in mediating direct damage to human vascular endothelial cells. , 1991, The Journal of infectious diseases.

[20]  D. Scheinberg,et al.  Monoclonal antibodies against Galα 1 −4Galß 1 −4Glc(Pk, CD77) produced with a synthetic glycoconjugate as immunogen: Reactivity with carbohydrates, with fresh frozen human tissues and hematopoietic tumors , 1991, International journal of cancer.

[21]  L. M. Sung,et al.  Acute renal tubular necrosis and death of mice orally infected with Escherichia coli strains that produce Shiga-like toxin type II , 1990, Infection and immunity.

[22]  M. Greaves,et al.  Expression of the CD34 gene in vascular endothelial cells. , 1990, Blood.

[23]  M. Hansen,et al.  Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. , 1989, Journal of immunological methods.

[24]  T. Yutsudo,et al.  Purification and some properties of a Vero toxin from a human strain of Escherichia coli that is immunologically related to Shiga-like toxin II (VT2). , 1989, Microbial pathogenesis.

[25]  S. Saxena,et al.  Shiga toxin, Shiga-like toxin II variant, and ricin are all single-site RNA N-glycosidases of 28 S RNA when microinjected into Xenopus oocytes. , 1989, The Journal of biological chemistry.

[26]  A. O’Brien,et al.  Isolation and characterization of monoclonal antibodies to Shiga-like toxin II of enterohemorrhagic Escherichia coli and use of the monoclonal antibodies in a colony enzyme-linked immunosorbent assay , 1988, Journal of clinical microbiology.

[27]  J. Brown,et al.  Direct cytotoxic action of Shiga toxin on human vascular endothelial cells , 1988, Infection and immunity.

[28]  L. Becker,et al.  The histopathology of the hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli infections. , 1988, Human pathology.

[29]  E. Ishii,et al.  Immunocytological and immunochemical analysis on the common acute lymphoblastic leukemia antigen (CALLA): evidence that CALLA on ALL cells and granulocytes are structurally related. , 1988, Hybridoma.

[30]  C. Lingwood,et al.  Glycolipid binding of purified and recombinant Escherichia coli produced verotoxin in vitro. , 1987, The Journal of biological chemistry.

[31]  J. Brown,et al.  The mode of action of Shiga toxin on peptide elongation of eukaryotic protein synthesis. , 1987, The Biochemical journal.

[32]  M. Noda,et al.  Purification and some properties of Shiga-like toxin from Escherichia coli O157:H7 that is immunologically identical to Shiga toxin. , 1987, Microbial pathogenesis.

[33]  J. Brown,et al.  Identification of the carbohydrate receptor for Shiga toxin produced by Shigella dysenteriae type 1. , 1987, The Journal of biological chemistry.

[34]  H. Collins,et al.  Morphologic evaluation of the effects of Shiga toxin and E coli Shiga-like toxin on the rabbit intestine. , 1986, The American journal of pathology.

[35]  G. Keusch,et al.  Pathogenesis of shigella diarrhea. XI. Isolation of a shigella toxin- binding glycolipid from rabbit jejunum and HeLa cells and its identification as globotriaosylceramide , 1986, The Journal of experimental medicine.

[36]  Y. Ishii,et al.  Characterization of two distinct antigens expressed on either resting or activated human B cells as defined by monoclonal antibodies. , 1986, Clinical and experimental immunology.

[37]  C. Pai,et al.  Experimental infection of infant rabbits with verotoxin-producing Escherichia coli , 1986, Infection and immunity.

[38]  R. Holmes,et al.  Characterization of monoclonal antibodies against Shiga-like toxin from Escherichia coli , 1985, Infection and immunity.

[39]  G. Keusch,et al.  Pathogenesis of Shigella diarrhea. IX. Simplified high yield purification of Shigella toxin and characterization of subunit composition and function by the use of subunit-specific monoclonal and polyclonal antibodies , 1984, The Journal of experimental medicine.

[40]  A. Michael,et al.  Stages of renal ontogenesis identified by monoclonal antibodies reactive with lymphohemopoietic differentiation antigens , 1983, The Journal of experimental medicine.

[41]  J. S. Fong,et al.  Hemolytic-Uremic Syndrome: Current Concepts and Management , 1982 .

[42]  D. Vazquez.  Inhibitors of protein synthesis , 1974, FEBS letters.

[43]  G. Keusch,et al.  The pathogenesis of Shigella diarrhea. I. Enterotoxin production by Shigella dysenteriae I. , 1972, The Journal of clinical investigation.

[44]  V. V. van Hinsbergh,et al.  Plasma cytokine levels in hemolytic uremic syndrome. , 1995, Nephron.

[45]  C. Lingwood.  Verotoxin-binding in human renal sections. , 1994, Nephron.

[46]  Lingwood Ca.  Verotoxins and their glycolipid receptors. , 1993 .

[47]  D. Harrison,et al.  Novel histopathologic findings in a surviving case of hemolytic uremic syndrome after bone marrow transplantation. , 1989, Human pathology.

[48]  T. Yutsudo,et al.  Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. RNA N-glycosidase activity of the toxins. , 1988, European journal of biochemistry.

[49]  H. Lior,et al.  The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. , 1985, The Journal of infectious diseases.