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. 1986 Jan;122(1):169–176.

Enhancement of endotoxin-induced isolated renal tubular cell injury by toxic shock syndrome toxin 1.

W F Keane, G Gekker, P M Schlievert, P K Peterson
PMCID: PMC1888123  PMID: 3079956

Abstract

The pathogenesis of toxic shock syndrome (TSS) remains unknown. On the basis of experimental data, it has been hypothesized that staphylococcal TSS Toxin 1 (TSST-1) may interact synergistically with low levels of endotoxin and give rise to many of the clinical findings. We have demonstrated previously that lipid A, the biologically active component of lipopolysaccharide (LPS), or endotoxin, induces dose-dependent necrosis of isolated rat renal tubular cells (RTCs). In the present studies, the authors investigated whether this injury could be augmented by TSST-1. The viability of RTCs was assessed by vital dye exclusion. Incubation of freshly isolated rat RTCs with either 1 ng/ml of TSST-1 or 0.1 ng/ml LPS or lipid A had minimal cytotoxicity (less than 6%). Exposure of RTCs to 1 ng/ml TSST-1 for 20 minutes, followed by washing, resulted in a significant enhancement of cytotoxicity when RTCs were exposed to 0.1 ng/ml LPS or lipid A. The sensitization of RTCs by TSST-1 to LPS- or lipid-A-induced injury was prevented by methylamine and chloroquine, two inhibitors of receptor-mediated endocytosis (RME). Chelation of extracellular calcium by 2 mM EGTA also blocked the TSST-1-induced sensitization of RTCs to LPS or lipid A. Inhibition of RTC arachidonic acid metabolism by methylprednisolone, indomethacin, ibuprofen, and piriprost significantly inhibited RTC necrosis induced by TSST-1 and LPS or lipid A by 33-62%. Thiourea and deferoxamine, agents which ameliorate oxidant injury, also inhibited this synergistic injury by 34-67%. Thus, TSST-1 enhanced the cytotoxic effects of LPS/lipid A, and the sensitization of RTCs appeared to involve RME or TSST-1. Oxidative metabolism of arachidonic acid and generation of reactive oxygen species appeared to participate in LPS/lipid-A-mediated RTC death.

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Selected References

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  1. Aggeler J., Werb Z. Initial events during phagocytosis by macrophages viewed from outside and inside the cell: membrane-particle interactions and clathrin. J Cell Biol. 1982 Sep;94(3):613–623. doi: 10.1083/jcb.94.3.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bergdoll M. S., Crass B. A., Reiser R. F., Robbins R. N., Lee A. C., Chesney P. J., Davis J. P., Vergeront J. M., Wand P. J. An enterotoxin-like protein in Staphylococcus aureus strains from patients with toxic shock syndrome. Ann Intern Med. 1982 Jun;96(6 Pt 2):969–971. doi: 10.7326/0003-4819-96-6-969. [DOI] [PubMed] [Google Scholar]
  3. Cade-Treyer D., Tsuji S. In vitro culture of the proximal tubule of the bovine nephron: transmission and scanning electron microscopy. Cell Tissue Res. 1975 Nov 17;163(1):15–28. doi: 10.1007/BF00218588. [DOI] [PubMed] [Google Scholar]
  4. Chesney R. W., Chesney P. J., Davis J. P., Segar W. E. Renal manifestations of the staphylococcal toxic-shock syndrome. Am J Med. 1981 Oct;71(4):583–588. doi: 10.1016/0002-9343(81)90210-2. [DOI] [PubMed] [Google Scholar]
  5. Davis J. P., Chesney P. J., Wand P. J., LaVenture M. Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention. N Engl J Med. 1980 Dec 18;303(25):1429–1435. doi: 10.1056/NEJM198012183032501. [DOI] [PubMed] [Google Scholar]
  6. Davis J. P., Vergeront J. M., Chesney P. J. Possible host-defense mechanisms in toxic shock syndrome. Ann Intern Med. 1982 Jun;96(6 Pt 2):986–991. doi: 10.7326/0003-4819-96-6-986. [DOI] [PubMed] [Google Scholar]
  7. FitzGerald D., Morris R. E., Saelinger C. B. Receptor-mediated internalization of Pseudomonas toxin by mouse fibroblasts. Cell. 1980 Oct;21(3):867–873. doi: 10.1016/0092-8674(80)90450-x. [DOI] [PubMed] [Google Scholar]
  8. Franson R. C., Eisen D., Jesse R., Lanni C. Inhibition of highly purified mammalian phospholipases A2 by non-steroidal anti-inflammatory agents. Modulation by calcium ions. Biochem J. 1980 Feb 15;186(2):633–636. doi: 10.1042/bj1860633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Graf E., Mahoney J. R., Bryant R. G., Eaton J. W. Iron-catalyzed hydroxyl radical formation. Stringent requirement for free iron coordination site. J Biol Chem. 1984 Mar 25;259(6):3620–3624. [PubMed] [Google Scholar]
  10. Hemler M. E., Lands W. E. Evidence for a peroxide-initiated free radical mechanism of prostaglandin biosynthesis. J Biol Chem. 1980 Jul 10;255(13):6253–6261. [PubMed] [Google Scholar]
  11. Ikejima T., Dinarello C. A., Gill D. M., Wolff S. M. Induction of human interleukin-1 by a product of Staphylococcus aureus associated with toxic shock syndrome. J Clin Invest. 1984 May;73(5):1312–1320. doi: 10.1172/JCI111334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kushnaryov V. M., Bergdoll M. S., MacDonald H. S., Vellinga J., Reiser R. Study of staphylococcal toxic shock syndrome toxin in human epithelial cell culture. J Infect Dis. 1984 Oct;150(4):535–545. doi: 10.1093/infdis/150.4.535. [DOI] [PubMed] [Google Scholar]
  13. Kushnaryov V. M., MacDonald H. S., Reiser R., Bergdoll M. S. Staphylococcal toxic shock toxin specifically binds to cultured human epithelial cells and is rapidly internalized. Infect Immun. 1984 Sep;45(3):566–571. doi: 10.1128/iai.45.3.566-571.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Larkin S. M., Williams D. N., Osterholm M. T., Tofte R. W., Posalaky Z. Toxic shock syndrome: clinical, laboratory, and pathologic findings in nine fatal cases. Ann Intern Med. 1982 Jun;96(6 Pt 2):858–864. doi: 10.7326/0003-4819-96-6-858. [DOI] [PubMed] [Google Scholar]
  15. Middlebrook J. L., Dorland R. B. Bacterial toxins: cellular mechanisms of action. Microbiol Rev. 1984 Sep;48(3):199–221. doi: 10.1128/mr.48.3.199-221.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Paller M. S., Hoidal J. R., Ferris T. F. Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest. 1984 Oct;74(4):1156–1164. doi: 10.1172/JCI111524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Paris A. L., Herwaldt L. A., Blum D., Schmid G. P., Shands K. N., Broome C. V. Pathologic findings in twelve fatal cases of toxic shock syndrome. Ann Intern Med. 1982 Jun;96(6 Pt 2):852–857. doi: 10.7326/0003-4819-96-6-852. [DOI] [PubMed] [Google Scholar]
  18. Parsonnet J., Hickman R. K., Eardley D. D., Pier G. B. Induction of human interleukin-1 by toxic-shock-syndrome toxin-1. J Infect Dis. 1985 Mar;151(3):514–522. doi: 10.1093/infdis/151.3.514. [DOI] [PubMed] [Google Scholar]
  19. Perry M. M., Gilbert A. B., Evans A. J. The structure of the germinal disc region of the hen's ovarian follicle during the rapid growth phase. J Anat. 1978 Oct;127(Pt 2):379–392. [PMC free article] [PubMed] [Google Scholar]
  20. Peterson P. K., Schlievert P. M., Conroy W., Kelly J. A., Spika J., Quie P. G. Protection against staphylococcal pyrogenic exotoxin type C-enhanced endotoxin lethality with methylprednisolone and IgG. J Infect Dis. 1983 Feb;147(2):358–358. doi: 10.1093/infdis/147.2.358. [DOI] [PubMed] [Google Scholar]
  21. Rodman J. S., Kerjaschki D., Merisko E., Farquhar M. G. Presence of an extensive clathrin coat on the apical plasmalemma of the rat kidney proximal tubule cell. J Cell Biol. 1984 May;98(5):1630–1636. doi: 10.1083/jcb.98.5.1630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schlievert P. M. Enhancement of host susceptibility to lethal endotoxin shock by staphylococcal pyrogenic exotoxin type C. Infect Immun. 1982 Apr;36(1):123–128. doi: 10.1128/iai.36.1.123-128.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schlievert P. M., Schoettle D. J., Watson D. W. Purification and physicochemical and biological characterization of a staphylococcal pyrogenic exotoxin. Infect Immun. 1979 Mar;23(3):609–617. doi: 10.1128/iai.23.3.609-617.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schlievert P. M., Shands K. N., Dan B. B., Schmid G. P., Nishimura R. D. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis. 1981 Apr;143(4):509–516. doi: 10.1093/infdis/143.4.509. [DOI] [PubMed] [Google Scholar]
  25. Shands K. N., Schmid G. P., Dan B. B., Blum D., Guidotti R. J., Hargrett N. T., Anderson R. L., Hill D. L., Broome C. V., Band J. D. Toxic-shock syndrome in menstruating women: association with tampon use and Staphylococcus aureus and clinical features in 52 cases. N Engl J Med. 1980 Dec 18;303(25):1436–1442. doi: 10.1056/NEJM198012183032502. [DOI] [PubMed] [Google Scholar]
  26. Trump B. F., Sato T., Trifillis A., Hall-Craggs M., Kahng M. W., Smith M. W. Cell and explant culture of kidney tubular epithelium. Methods Cell Biol. 1980;21B:309–326. doi: 10.1016/s0091-679x(08)60689-5. [DOI] [PubMed] [Google Scholar]
  27. Vergeront J. M., Stolz S. J., Crass B. A., Nelson D. B., Davis J. P., Bergdoll M. S. Prevalence of serum antibody to staphylococcal enterotoxin F among Wisconsin residents: implications for toxic-shock syndrome. J Infect Dis. 1983 Oct;148(4):692–698. doi: 10.1093/infdis/148.4.692. [DOI] [PubMed] [Google Scholar]

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