Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Aug;64(8):3267–3272. doi: 10.1128/iai.64.8.3267-3272.1996

Proteins of 30 and 36 kilodaltons, membrane constituents of the Staphylococcus aureus L form, induce production of tumor necrosis factor alpha and activate the human immunodeficiency virus type 1 long terminal repeat.

A Akashi 1, S Ono 1, K Kuwano 1, S Arai 1
PMCID: PMC174217  PMID: 8757863

Abstract

We have previously demonstrated that the membrane of the Staphylococcus aureus L form induced tumor necrosis factor alpha (TNF-alpha) from murine macrophages. In this study, we purified two proteins which induce TNF-alpha production from a human monocytic cell line, THP-1, and murine macrophages. These molecules were purified from delipidated membranes by deoxycholic acid extraction, two-step anion-exchange chromatography, and preparative electrophoresis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified proteins showed for each a single band with a molecular mass of 30, and 36 kDa. These proteins were heat stable. Polymyxin B did not affect the production of TNF-alpha induced by these proteins. Furthermore, these proteins induced comparable levels of TNF-alpha in both lipopolysaccharide-responsive and -nonresponsive mouse macrophages. Pretreatment of murine macrophages with gamma interferon enhanced 30- and 36-kDa protein-mediated TNF-alpha production. The 30-kDa protein showed lethal toxicity to D-galactosamine-treated mice. The 30- and 36-kDa proteins stimulated the human immunodeficiency virus type 1 long terminal repeat in a monocytic cell line but not a T-cell line. This effect appeared to be mediated through the induction of nuclear factor kappaB. These results indicate that the 30- and 36-kDa proteins, membrane constituents of the S. aureus L form, may play a role in S. aureus infection and/or in human immunodeficiency virus type 1-infected individuals.

Full Text

The Full Text of this article is available as a PDF (303.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arai S., Furukawa M., Munakata T., Kuwano K., Inoue H., Miyazaki T. Enhancement of cytotoxicity of active macrophages by mycoplasma: role of mycoplasma-associated induction of tumor necrosis factor-alpha (TNF-alpha) in macrophages. Microbiol Immunol. 1990;34(3):231–243. doi: 10.1111/j.1348-0421.1990.tb01006.x. [DOI] [PubMed] [Google Scholar]
  2. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  3. Belsheim M. R., Darwish R. Z., Watson W. C., Schieven B. Bacterial L-form isolation from inflammatory bowel disease patients. Gastroenterology. 1983 Aug;85(2):364–369. [PubMed] [Google Scholar]
  4. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  5. Bhakdi S., Klonisch T., Nuber P., Fischer W. Stimulation of monokine production by lipoteichoic acids. Infect Immun. 1991 Dec;59(12):4614–4620. doi: 10.1128/iai.59.12.4614-4620.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bone R. C. Gram-positive organisms and sepsis. Arch Intern Med. 1994 Jan 10;154(1):26–34. [PubMed] [Google Scholar]
  7. Burchett S. K., Weaver W. M., Westall J. A., Larsen A., Kronheim S., Wilson C. B. Regulation of tumor necrosis factor/cachectin and IL-1 secretion in human mononuclear phagocytes. J Immunol. 1988 May 15;140(10):3473–3481. [PubMed] [Google Scholar]
  8. Carro T., Pedersen N. C., Beaman B. L., Munn R. Subcutaneous abscesses and arthritis caused by a probable bacterial L-form in cats. J Am Vet Med Assoc. 1989 Jun 1;194(11):1583–1588. [PubMed] [Google Scholar]
  9. Collart M. A., Belin D., Vassalli J. D., de Kossodo S., Vassalli P. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med. 1986 Dec 1;164(6):2113–2118. doi: 10.1084/jem.164.6.2113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fischer H., Dohlsten M., Andersson U., Hedlund G., Ericsson P., Hansson J., Sjögren H. O. Production of TNF-alpha and TNF-beta by staphylococcal enterotoxin A activated human T cells. J Immunol. 1990 Jun 15;144(12):4663–4669. [PubMed] [Google Scholar]
  11. Fong Y., Tracey K. J., Moldawer L. L., Hesse D. G., Manogue K. B., Kenney J. S., Lee A. T., Kuo G. C., Allison A. C., Lowry S. F. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med. 1989 Nov 1;170(5):1627–1633. doi: 10.1084/jem.170.5.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Freudenberg M. A., Galanos C. Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. Infect Immun. 1991 Jun;59(6):2110–2115. doi: 10.1128/iai.59.6.2110-2115.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Galanos C., Freudenberg M. A., Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5939–5943. doi: 10.1073/pnas.76.11.5939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Glauser M. P., Heumann D., Baumgartner J. D., Cohen J. Pathogenesis and potential strategies for prevention and treatment of septic shock: an update. Clin Infect Dis. 1994 Feb;18 (Suppl 2):S205–S216. doi: 10.1093/clinids/18.supplement_2.s205. [DOI] [PubMed] [Google Scholar]
  15. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hayes M. P., Zoon K. C. Priming of human monocytes for enhanced lipopolysaccharide responses: expression of alpha interferon, interferon regulatory factors, and tumor necrosis factor. Infect Immun. 1993 Aug;61(8):3222–3227. doi: 10.1128/iai.61.8.3222-3227.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Herbelin A., Ruuth E., Delorme D., Michel-Herbelin C., Praz F. Mycoplasma arginini TUH-14 membrane lipoproteins induce production of interleukin-1, interleukin-6, and tumor necrosis factor alpha by human monocytes. Infect Immun. 1994 Oct;62(10):4690–4694. doi: 10.1128/iai.62.10.4690-4694.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heumann D., Barras C., Severin A., Glauser M. P., Tomasz A. Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes. Infect Immun. 1994 Jul;62(7):2715–2721. doi: 10.1128/iai.62.7.2715-2721.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jacobson M. A., Gellermann H., Chambers H. Staphylococcus aureus bacteremia and recurrent staphylococcal infection in patients with acquired immunodeficiency syndrome and AIDS-related complex. Am J Med. 1988 Aug;85(2):172–176. doi: 10.1016/s0002-9343(88)80337-1. [DOI] [PubMed] [Google Scholar]
  20. Kagan G. Y., Koptelova E. I., Pokrovsky B. M. Isolation of pleuropneumonia-like organisms, L-forms and heteromorphous growth of bacteria from the cerebrospinal fluid of patients with septic meningitis. J Hyg Epidemiol Microbiol Immunol. 1965;9(3):310–317. [PubMed] [Google Scholar]
  21. Keller R., Fischer W., Keist R., Bassetti S. Macrophage response to bacteria: induction of marked secretory and cellular activities by lipoteichoic acids. Infect Immun. 1992 Sep;60(9):3664–3672. doi: 10.1128/iai.60.9.3664-3672.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Krumholz H. M., Sande M. A., Lo B. Community-acquired bacteremia in patients with acquired immunodeficiency syndrome: clinical presentation, bacteriology, and outcome. Am J Med. 1989 Jun;86(6 Pt 2):776–779. doi: 10.1016/0002-9343(89)90472-5. [DOI] [PubMed] [Google Scholar]
  23. Kuwano K., Akashi A., Matsu-ura I., Nishimoto M., Arai S. Induction of macrophage-mediated production of tumor necrosis factor alpha by an L-form derived from Staphylococcus aureus. Infect Immun. 1993 May;61(5):1700–1706. doi: 10.1128/iai.61.5.1700-1706.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Levine S. J., White D. A., Fels A. O. The incidence and significance of Staphylococcus aureus in respiratory cultures from patients infected with the human immunodeficiency virus. Am Rev Respir Dis. 1990 Jan;141(1):89–93. doi: 10.1164/ajrccm/141.1.89. [DOI] [PubMed] [Google Scholar]
  26. Mathison J. C., Wolfson E., Ulevitch R. J. Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest. 1988 Jun;81(6):1925–1937. doi: 10.1172/JCI113540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  28. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Parsonnet J., Gillis Z. A. Production of tumor necrosis factor by human monocytes in response to toxic-shock-syndrome toxin-1. J Infect Dis. 1988 Nov;158(5):1026–1033. doi: 10.1093/infdis/158.5.1026. [DOI] [PubMed] [Google Scholar]
  30. Pomerantz R. J., Feinberg M. B., Trono D., Baltimore D. Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression. J Exp Med. 1990 Jul 1;172(1):253–261. doi: 10.1084/jem.172.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Raviglione M. C., Battan R., Pablos-Mendez A., Aceves-Casillas P., Mullen M. P., Taranta A. Infections associated with Hickman catheters in patients with acquired immunodeficiency syndrome. Am J Med. 1989 Jun;86(6 Pt 2):780–786. doi: 10.1016/0002-9343(89)90473-7. [DOI] [PubMed] [Google Scholar]
  32. Roulston A., Lin R., Beauparlant P., Wainberg M. A., Hiscott J. Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B/Rel transcription factors. Microbiol Rev. 1995 Sep;59(3):481–505. doi: 10.1128/mr.59.3.481-505.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. See R. H., Kum W. W., Chang A. H., Goh S. H., Chow A. W. Induction of tumor necrosis factor and interleukin-1 by purified staphylococcal toxic shock syndrome toxin 1 requires the presence of both monocytes and T lymphocytes. Infect Immun. 1992 Jul;60(7):2612–2618. doi: 10.1128/iai.60.7.2612-2618.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Shakhov A. N., Collart M. A., Vassalli P., Nedospasov S. A., Jongeneel C. V. Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J Exp Med. 1990 Jan 1;171(1):35–47. doi: 10.1084/jem.171.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Timmerman C. P., Mattsson E., Martinez-Martinez L., De Graaf L., Van Strijp J. A., Verbrugh H. A., Verhoef J., Fleer A. Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans. Infect Immun. 1993 Oct;61(10):4167–4172. doi: 10.1128/iai.61.10.4167-4172.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  37. Wessel D., Flügge U. I. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem. 1984 Apr;138(1):141–143. doi: 10.1016/0003-2697(84)90782-6. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES