The effects of triterpene glycosides and phospholipids from marine invertebrates in the composition of tubular immunostimulating complexes on the immunogenicity of human serum albumin

Russian Journal of Marine Biology - Tập 41 - Trang 69-77 - 2015
N. S. Vorobyeva1, A. N. Mazeika1, L. A. Davydova1, P. V. Velansky1, A. V. Tsybulsky1, E. Y. Kostetsky1, N. M. Sanina1
1Far Eastern Federal University, Vladivostok, Russia

Tóm tắt

To study the adjuvant activity and to optimize tubular immunostimulating complexes (TI complexes) with respect to the soluble antigen, an investigation was performed on cucumariosides and their fractions, i.e., individual triterpene glycosides that were obtained from the holothurian Cucumaria japonica, as well as on phospholipids from the sea urchin Strongylocentrotus intermedius and the starfish Distolasterias nippon included in the composition of TI complexes in order to assess their effects on the immunogenicity of human serum albumin (HSA). Generally, TI complexes showed a moderate adjuvant activity with respect to HSA; this activity can be adjusted by substitution of a cucumarioside and/or a polar lipid in the composition of the TI complex. TI complexes based on monogalactosyldyacylglycerol (MGDG) from the sea alga Ulva lactuca and cucumariosides A2-2 and A4-4 maximally stimulated anti-HSA antibody production in mice. Substitution of MGDG for phosphatidylcholine (PC) from the starfish D. nippon with an increased (compared with other investigated phospholipids) ratio of n-3/n-6 polyunsaturated fatty acids did not result in a change in the immunostimulating activity of the TI complex. However, the use of other phospholipids led to a decrease in the adjuvant activity of the TI complex, compared with that of the TI complex based on PC from D. nippon and cucumarioside A2-2. The greatest fluctuations in the contents of cytokines IL-6, IL-12, IFN-γ and GM-CSF depending on the composition of the TI complexes indicate the possibility of regulation of the T-cell immune response. The values of hematological parameters were normal.

Tài liệu tham khảo

Avilov, S.A., Stonik V.A., and Kalinovskii, A.I., The structure of four new triterpene glycosides from the holothurian Cucumaria japonica, Khim. Prir. Soedin., 1990, no. 6, pp. 787–792. Kalinin, V.I., Levin, V.S., and Stonik, V.A., Khimicheskaya morfologiya: triterpenovyye glikozidy goloturii (Chemical Morphology: Triterpene Glycosides of Holothurians (Holothurioidea, Echinodermata)), Vladivostok: Dal’nauka, 1994. Kostetsky, E.Ya., Sanina, N.M., Mazeika A.N., et al., RF Patent 2 446 822, 2012. Nazarenko, G.I. and Kishkur, A.A., Klinicheskaya otsenka rezul’tatov laboratornykh issledovanii (Clinical Evaluation of Laboratory Results), Moscow: Medicine, 2006. Portnyagina, O.Yu., Novikova, O.D., Vostrikova, O.P., et al., The dynamics of the immune response to outer membrane porins from Yersinia pseudotuberculosis, Zh. Mikrobiol. Epidemiol. Immunobiol., 1999, vol. 128, no. 10, pp. 437–440. Aguilar, J.C. and Rodríguez, E.G., Vaccine adjuvants revisited, Vaccine, 2007, vol. 25, pp. 3752–3762. Antoine-Moussiaux, N., Saerens, D., and Desmecht, D., Flow cytometric enumeration of parasitaemia and haematologic changes in trypanosomainfected mice, Acta Trop., 2008, vol. 107, no. 2, pp. 139–144. Harbige, L.S., Fatty acids, the immune response, and autoimmunity: a question of n-6 essentiality and the balance between n-6 and n-3, Lipids, 2003, vol. 38, no. 4, pp. 323–341. Kersten, G.F. and Crommelin, D.J., Liposomes and ISCOMS as vaccine formulations, Biochim. Biophys. Acta, 1995, vol. 1241, pp. 117–138. Kostetsky, E.Y., Sanina, N.M., Mazeika, A.N., et al., Tubular immunostimulating complex based on A2-2 and monogalactosyldiacylglycerol from marine macrophytes, J. Nanobiotechnol., 2011., vol. 9, no. 35, doi: 10.1186/1477-3155-9-35. Morein, B. and Bengtsson, K.L., Immunomodulation by iscoms, immune stimulating complexes, Methods, 1999, vol. 19, pp. 94–102. Newport, M., The genetics of nontuberculous mycobacterial infection, Exp. Rev. Mol. Med., 2003, vol. 5, no. 6, pp. 1–13. Pearse, M.J. and Drane, D., ISCOMATRIX® adjuvant for antigen delivery, Adv. Drug Deliv. Rev., 2005, vol. 57, no. 3, pp. 465–474. Sanders, M.T., Brown, L.E., Deliyannis, G., and Pearse, M.J., ISCOM-based vaccines: the second decade, Immunol. Cell Biol., 2005, vol. 83, no. 2, pp. 119–128. Sanina, N.M., Goncharova, S.N., and Kostetsky, E.Y., Seasonal change of fatty acid composition and thermotropic behavior of polar lipids from marine macrophytes, Phytochemistry, 2008, vol. 69, pp. 1517–1527. Sanina, N.M. and Kostetsky, E.Y., Thermotropic behavior of major phospholipids from marine invertebrates: changes with warm-acclimation and seasonal acclimatization, Comp. Biochem. Physiol., Part B: Biochem. Mol. Biol., 2002, vol. 133, pp. 143–153. Sanina, N.M., Kostetsky, E.Y., Shnyrov, V.L., et al., The influence of monogalactosyldiacylglycerols from different marine macrophytes on immunogenicity and conformation of protein antigen of tubular immunostimulating complex, Biochimie, 2012, vol. 94, pp. 1048–1056. Shaikh, S.R. and Edidin, M., Polyunsaturated fatty acids, membrane organization, T cells, and antigen presentation, Am. J. Clin. Nutr., 2006, vol. 84, pp. 1277–1289. Sjolander, D., Drane, E., Maraskovsky, J.P., et al., Immune responses to ISCOM formulations in animal and primate models, Vaccine, 2001, vol. 19, pp. 2661–2665. Skene, C.D. and Sutton, P., Saponin-adjuvanted particulate vaccines for clinical use, Methods, 2006, vol. 40, pp. 53–59. Svetashev, V.I. and Vaskovsky, V.E., A simplified technique for thin-layer microchromatography of lipids, J. Chromatogr., 1972, vol. 67, pp. 376–378. Yaqoob, P., Fatty acids as gatekeepers of immune cell regulation, Trends Immunol., 2003, vol. 24, pp. 639–645.