INDUCTION AND PROTECTIVE PROPERTIES OF ANTIBODIES AGAINST MURAMYL PEPTIDES OF GRAM-NEGATIVE BACTERIA


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Abstract

Aim. Characterize the role of humoral immune response in mechanisms of action of muramyl dipeptide immune stimulators. Materials and methods. Mice were immunized by a complex of muramyl peptides (CMP) obtained from Salmonella typhi peptidoglycan and consisting of 3 components: 1) N-acetyl-D-glucoasminyl-(β1→4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelic acid (GMtri); 2) N-acetyl-D-glucosaminyl-(β1→4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimeloyl-D-alanine (GMtetra) and 3) GMtetra dimer (diGMtetra), in which monomeric residues of GMtetra are linked by an amid bond between carboxyl group of terminal D-alanine of one of GMtetra residues and ω-amino group of meso-diaminopimelic acid of the other GMtetra residue. Results. Immunization resulted in a multifold increase of IgM, IgG1 and IgG2a titers against CMP. Antibodies were directed against the whole molecule of diGMtetra and did not recognize its fragments. Sera of mice immunized with CMP protected the mice from lethal infection with Gram-negative (S. typhimurium) but not Gram-positive (Staphylococcus aureus) microorganisms. Conclusion. Induction of protective antibodies may present a novel mechanism of action of muramyl dipeptide immune stimulators.

About the authors

M. V Paschenkov

State Scientific Centre - Institute of Immunology, Moscow, Russia

V. G Pak

State Scientific Centre - Institute of Immunology, Moscow, Russia

B. I Alkhazova

State Scientific Centre - Institute of Immunology, Moscow, Russia

V. L Lvov

State Scientific Centre - Institute of Immunology, Moscow, Russia

B. V Pinegin

State Scientific Centre - Institute of Immunology, Moscow, Russia

References

  1. Пащенков М.В., Попилюк С.Ф., Алхазова Б.И. и др. Иммунобиологические свойства мурамилпептидных фрагментов пептидогликана грамотрицательных бактерий. Иммунология. 2010, 31: 119-125.
  2. Пащенков М.В., Будихина А.С., Голубева Н.М. и др. Результаты I фазы клинических испытаний иммуномодулятора «Полимурамил». Иммунология. 2011, 32: 239-243.
  3. Пащенков М.В., Будихина А.С., Голубева Н.М. и др. Клиническая и иммунологическая эффективность иммуномодулятора Полимурамил при гнойной хирургической инфекции. Физиология и патология иммунной системы. Иммунофармакогеномика. 2011, 15: 12-18.
  4. Azuma I. Development of the cytokine inducer romurtide: experimental studies and clinical application. Trends Pharmacol Sci. 1992, 13: 425-428.
  5. Capparelli R., Nocerino N., Medaglia C. et al. The Staphylococcus aureus peptidoglycan protects mice against the pathogen and eradicates experimentally induced infection. PLoS One. 2011, 6: e28377.
  6. Chamaillard M., Hashimoto M., Horie Y. et al. An essential role for NOD1 in host recognition ofbacterial peptidoglycan containing diaminopimelic acid. Nat. Immunol. 2003,4:702-707.
  7. Dziarski R., Gupta D. Staphylococcus aureus peptidoglycan is a toll-like receptor 2 activator: a reevaluation. Infect. Immun. 2005, 73: 5212-5216.
  8. Ellouz F., Adam A., Ciorbaru R. et al. Minimal structural requirements for adjuvant activity ofbacterial peptidoglycan derivatives. Biochem. Biophys. Res. Commun. 1974, 59:1317-1325.
  9. Franken N., Seidl P.H., Kuchenbauer T. et al. Specific immunoglobulin A antibodies to a peptide subunit sequence ofbacterial cell wall peptidoglycan. Infect. Immun. 1984, 44: 182-187.
  10. Franken N., Seidl P.H., Zauner E. et al. Quantitative determination of human IgG antibodies to the peptide subunit determinant of peptidoglycan by an enzyme-linked immunosorbent assay. Mol. Immunol. 1985, 22: 573-579.
  11. Fritz J.H., Le Bourhis L., Sellge G. et al. Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity. Immunity. 2007, 26: 445-459.
  12. Girardin S.E., Boneca I.G., Viala J. et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem. 2003, 278: 88698872.
  13. Hardy R.R. B-1 B cells: development, selection, natural autoantibody and leukemia. Curr Opin. Immunol. 2006, 18: 547-555.
  14. Magalhaes J.G., Fritz J.H., Le Bourhis L. et al. Nod2-dependent Th2 polarization of antigen-specific immunity. J. Immunol. 2008, 181: 7925-7935.
  15. Martin F., Kearney J.F. B1 cells: similarities and differences with other B cell subsets. Curr. Opin. Immunol. 2001, 13: 195-201.
  16. Meshcheryakova E., Makarov E., Philpott D. et al. Evidence for correlation between the intensities of adjuvant effects and NOD2 activation by monomeric, dimeric and lipophylic derivatives of N-acetylglucosaminyl-N-acetylmuramyl peptides. Vaccine. 2007, 25:4515-4520.
  17. Nardin A., Lefebvre M.L., Labroquere K. et al. Liposomal muramyl tripeptide phos-phatidylethanolamine: Targeting and activating macrophages for adjuvant treatment of osteosarcoma. Curr. Cancer Drug Targets. 2006, 6: 123-133.
  18. Pashenkov M.V., Popilyuk S.F., Alkhazova B.I. et al. Muropeptides trigger distinct activation profiles in macrophages and dendritic cells. Int. Immunopharmacol. 2010, 10: 875-882.
  19. Pinegin B.V., Kulakov A.V., Makarov E.A. et al. The occurrence of natural antibodies to minimal component of bacterial cell wall (N-acetylglucosaminyl-N-acetylmuramyl dipeptide) in sera from healthy humans. Immunol. Lett. 1995, 47: 33-37.
  20. Schleifer K.H., Kandler O. Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol. Rev. 1972, 36: 407-477.
  21. Wergeland H.I., Endresen C. Antibodies to various bacterial cell wall peptidoglycans in human and rabbit sera. J. Clin. Microbiol. 1987, 25: 540-545.
  22. Zeiger A.R., Tuazon C.U., Sheagren J.N. Antibody levels to bacterial peptidoglycan in human sera during the time course ofendocarditis and bacteremic infections caused by Staphylococcus aureus. Infect. Immun. 1981, 33: 795-800.

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Copyright (c) 2013 Paschenkov M.V., Pak V.G., Alkhazova B.I., Lvov V.L., Pinegin B.V.

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