1887

Abstract

type B strain produces two forms of progenitor toxin, 16S and 12S. The 12S toxin is formed by association of a neurotoxin (NTX) and a non-toxic non-haemagglutinin (NTNH), and the 16S toxin is formed by conjugation of the 12S toxin with a haemagglutinin (HA). HA consists of four subcomponents designated HA1, HA2, HA3a and HA3b. When mice were immunized with formalin-detoxified NTX, 12S or 16S, a significantly greater amount of anti-NTX antibody (Ab) was produced in the mice injected with 16S than in NTX- or 12S-injected mice. Immunization with NTX mixed with HA1 and/or HA3b also increased the anti-NTX Ab production, whereas NTX mixed with HA2 did not, indicating that HA1 and HA3b have adjuvant activity. This was further confirmed by immunizing mice with human albumin (Alb) alone or Alb mixed with either HA1 or HA3b. When mouse-spleen cells were stimulated with NTX, 16S or different HA subcomponents, 16S, HA1, HA3b and the mixture of HA1 and HA3 significantly increased interleukin 6 (IL6) production compared with NTX alone. Transcription of IL6 mRNA was low after stimulation with NTX alone, but increased to 16S-stimulation levels when NTX was mixed with HA1 or HA3b. In flow cytometry using labelled Abs against CD3 and CD19, the percentage of CD19 cells was higher following stimulation with 16S or NTX mixed with HA1 or HA3b compared with stimulation with NTX. The percentage of CD3 cells remained unchanged. These results suggest strongly that HA1 and HA3b demonstrate adjuvant activity via increasing IL6 production.

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.28421-0
2005-11-01
2020-10-01
Loading full text...

Full text loading...

/deliver/fulltext/micro/151/11/3739.html?itemId=/content/journal/micro/10.1099/mic.0.28421-0&mimeType=html&fmt=ahah

References

  1. Arbibe L., Mira J.-P., Teusch N., Kline L., Guha M., Mackman N., Godowski P. J., Ulevitch R. J., Knaus U. G. 2000; Toll-like receptor 2-mediated NF- κ B activation requires a Rac1-dependent pathway. Nat Immunol1:533–540[CrossRef]
    [Google Scholar]
  2. Arimitsu H., Inoue K., Sakaguchi Y., Lee J., Fujinaga Y., Watanabe T., Ohyama T., Hirst R., Oguma K. 2003; Purification of fully activated Clostridium botulinum serotype B toxin for treatment of patients with dystonia. Infect Immun71:1599–1603[CrossRef]
    [Google Scholar]
  3. Bach E. A., Aguet M., Schreiber R. D. 1997; The IFN γ receptor: a paradigm for cytokine receptor signaling. Annu Rev Immunol15:563–591[CrossRef]
    [Google Scholar]
  4. Birkenkamp K. U., Esselink M. T., Kruijer W., Vellenga E. 2000; An inhibitor of PI3-K differentially affects proliferation and IL-6 protein secretion in normal and leukemic myeloid cells depending on the stage of differentiation. Exp Hematol28:1239–1249[CrossRef]
    [Google Scholar]
  5. Bode J. G., Peters-Regehr T., Schliess F., Häussinger D. 1998; Activation of mitogen-activated protein kinases and IL-6 release in response to lipopolysaccharides in Kupffer cells is modulated by anisoosmolarity. J Hepatol28:795–802[CrossRef]
    [Google Scholar]
  6. Dahle M. K., Øverland G., Myhre A. E., Stuestøl J. F., Hartung T., Krohn C. D., Mathiesen Ø., Wang J. E., Aasen A. O. 2004; The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10. Infect Immun72:5704–5711[CrossRef]
    [Google Scholar]
  7. de Haan L. D., Hearn A. R., Rivett A. J., Hirst T. R. 2002; Enhanced delivery of exogenous peptides into the class I antigen processing and presentation pathway. Infect Immun70:3249–3258[CrossRef]
    [Google Scholar]
  8. Dressler D., Bigalke H., Bencke R. 2003; Botulinum toxin type B in antibody-induced botulinum toxin type A therapy failure. J Neurol250:967–969 corrected and republished as J Neurol 250, 1263–1265
    [Google Scholar]
  9. Fujinaga Y., Inoue K., Shimazaki S.. 8 other authors 1994; Molecular construction of Clostridium botulinum type C progenitor toxin and its gene organization. Biochem Biophys Res Commun205:1291–1298[CrossRef]
    [Google Scholar]
  10. Fujinaga Y., Inoue K., Nomura T., Sasaki J., Marvard J. C., Popoff M. R., Kozaki S., Oguma K. 2000; Identification and characterization of functional subunits of Clostridium botulinum type A progenitor toxin involved in binding to intestinal microvilli and erythrocytes. FEBS Lett467:179–183[CrossRef]
    [Google Scholar]
  11. Fujinaga Y., Inoue K., Watarai S.. 10 other authors 2004; Molecular characterization of binding subcomponents of Clostridium botulinum type C progenitor toxin for intestinal epithelial cells and erythrocytes. Microbiology150:1529–1538[CrossRef]
    [Google Scholar]
  12. Gao B., Tsan M.-F. 2003; Recombinant human heat shock protein 60 does not induce the release of tumor necrosis factor α from murine macrophages. J Biol Chem278:22523–22529[CrossRef]
    [Google Scholar]
  13. Herrmann J., Geth K., Mall V.. 8 other authors 2004; Clinical impact of antibody formation to botulinum toxin A in children. Ann Neurol55:732–735[CrossRef]
    [Google Scholar]
  14. Hirano T. 1998; Interleukin 6 and its receptor: ten years later. Int Rev Immunol16:249–284[CrossRef]
    [Google Scholar]
  15. Inoue K., Fujinaga Y., Watanabe T., Ohyama T., Takeshi K., Moriishi K., Nakajima H., Inoue K., Oguma K. 1996; Molecular composition of Clostridium botulinum type A progenitor toxins. Infect Immun64:1589–1594
    [Google Scholar]
  16. Inoue K., Fujinaga Y., Honke K.. 7 other authors 2001; Clostridium botulinum type A haemagglutinin-positive progenitor toxin (HA+-PTX) binds to oligosaccharides containing Gal β 1-4GlcNAc through one subcomponent of haemagglutinin (HA1). Microbiology147:811–819
    [Google Scholar]
  17. Inoue K., Sobhany M., Transue T. R., Oguma K., Pedersen L. C., Negishi M. 2003; Structural analysis by X-ray crystallography and calorimetry of a haemagglutinin component (HA1) of the progenitor toxin from Clostridium botulinum . Microbiology149:3361–3370[CrossRef]
    [Google Scholar]
  18. Jankovic J., Brin M. F. 1991; Therapeutic uses of botulinum toxin. N Engl J Med324:1186–1194[CrossRef]
    [Google Scholar]
  19. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227:680–685[CrossRef]
    [Google Scholar]
  20. Nishikawa A., Uotsu N., Arimitsu H.. 8 other authors 2004; The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells. Biochem Biophys Res Commun319:327–333[CrossRef]
    [Google Scholar]
  21. Oguma K., Inoue K., Fujinaga Y., Yokota K., Watanabe T., Ohyama T., Takeshi K., Inoue K. 1999; Structure and function of Clostridium botulinum progenitor toxin. J Toxicol Toxin Rev18:17–34[CrossRef]
    [Google Scholar]
  22. Paul W. E. 1991; Interleukin-4: a prototypic immunoregulatory lymphokine. Blood77:1859–1870
    [Google Scholar]
  23. Schantz E. J., Johnson E. A. 1994; Preparation and characterization of botulinum toxin type A for human treatment. In Therapy with Botulinum Toxin pp41–49 Edited by Jankovic J., Hallett M.. New York: Marcel Dekker;
    [Google Scholar]
  24. Scott A. B. 1980; Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology87:1044–1049[CrossRef]
    [Google Scholar]
  25. Sugiyama H. 1980; Clostridium botulinum neurotoxin. Microbiol Rev44:419–448
    [Google Scholar]
  26. Tuyt L. M. L., Dokter W. H. A., Birkenkamp K., Koopmans S. B., Lummen C., Kruijer W., Vellenga E. 1999; Extracellular-regulated kinase 1/2, Jun N-terminal kinase, and c-Jun are involved in NF- κ B-dependent IL-6 expression in human monocytes. J Immunol162:4893–4902
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.28421-0
Loading
/content/journal/micro/10.1099/mic.0.28421-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error