Bioactive Components of Milk pp 241-250

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 606) | Cite as

A Proline-Rich Polypeptide from Ovine Colostrum: Colostrinin with Immunomodulatory Activity

  • Michal Zimecki

Abstract

A proline-rich polypeptide (PRP), later called colostrinin (CLN), was originally found as a fraction accompanying sheep colostral immunoglobulins. Extensive in vitro and in vivo studies in mice revealed its interesting T cell-tropic activities. The polypeptide promoted T cell maturation from early thymic precursors that acquired the phenotype and function of mature, helper cells; on the other hand, it also affected the phenotype and function of mature T cells. In particular, PRP was shown to recruit suppressor T cells in a model of T cell-independent humoral immune response and suppressed autoimmune hemolytic anemia in New Zealand Black mice. Subsequent in vitro studies in the human model revealed that CLN regulated mitogen-induced cytokine production in whole blood cultures. A discovery that CLN promoted procognitive functions in experimental animal models, supported by other laboratory findings, indicating prevention of pathological processes in the central nervous system, led to application of CLN in multicenter clinical trials. The trials demonstrated the therapeutic benefit of CLN in Alzheimer’s disease (AD) patients by delaying progress of the disease.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Basci, A., Stanton, J. G., Hughes, T. K., Kruzel, M., & Boldogh, I. (2005). Colostrinin-driven neurite outgrowth requires p53 activation in PC12 cells. Cellular and Molecular Neurobiology, 25, 1123–1139.CrossRefGoogle Scholar
  2. Bacsi, A., Aguilera-Aguirre, L., German, P., Kruzel, M., & Boldogh, I. (2006). Colostrinin decreases spontaneous and induced mutation frequencies at the Hprt locus in Chinese hamster V79 cells. Journal of Experimental Therapeutics and Oncology, 5, 249–259.Google Scholar
  3. Bilikiewicz, A., & Gaus, W. (2004). Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer’s disease. Journal of Alzheimer’s Disease, 6, 17–26.Google Scholar
  4. Boldogh, I., Liebenthal, D., Hughes, K., Juelich, T. L., Georgiades, J. A., Kruzel, M. L., & Stanton, G. J. (2003). Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. Journal of Molecular Neuroscience, 20, 125–133.CrossRefGoogle Scholar
  5. Bourhim, M., Kruzel, M., Srikrishnan, T., & Nicotera, T. (2006). Linear quantitation of Aβ aggregation using Thioflavin T: Reduction of fibril formation by Colostrinin. Journal of Neuroscience Methods, in press.Google Scholar
  6. Hraba, T., Wieczorek, Z., Janusz, M., Lisowski, J., & Zimecki, M. (1986). Effect of proline-rich polypeptide on experimental autoimmune response to erythrocytes. Archivum Immunologiae et Therapiae Experimentalis, 34, 437–443.Google Scholar
  7. Inglot, A. D., Janusz, M., & Lisowski, J. (1996). Colostrinine: A proline-rich polypeptide from ovine colostrum is a modest cytokine inducer in human leukocytes. Archivum Immunologiae et Therapiae Experimentalis, 44, 215–224.Google Scholar
  8. Janusz, M., Starościk, K., Zimecki, M., Wieczorek, Z., & Lisowski, J. (1978). Physicochemical properties of a proline-rich polypeptide (PRP) from ovine colostrum. Archivum Immunologiae et Therapiae Experimentalis, 26, 17–21.Google Scholar
  9. Janusz, M., Starościk, K., Zimecki, M., Wieczorek, Z., & Lisowski, J. (1981). Chemical and physical characterization of a proline-rich polypeptide from sheep colostrum. Biochemical Journal, 199, 9–15.Google Scholar
  10. Janusz, M., Starościk, K., Zimecki, M., Wieczorek, Z., & Lisowski, J. (1986). A proline-rich polypeptide (PRP) with immunoregulatory properties isolated from ovine colostrums. Murine thymocytes have on their surface a receptor specific for PRP. Archivum Immunologiae et Therapiae Experimentalis, 34, 427–436.Google Scholar
  11. Kruzel, M., Janusz, M., Lisowski, J., Fischleigh, R. V., & Georgiades, J. A. (2001). Towards an understanding of biological role of Colostrinin peptides. Journal of Molecular Neuroscience, 17, 379–389.CrossRefGoogle Scholar
  12. Kruzel, M. L., Polanowski, A., Wilusz, T., Sokołowska, A., Pacewicz, M., Bednarz, R., & Georgiades, J. A. (2004). The alcohol-induced conformational changes in casein micelles: A new challenge for the purification of Colostrinin. The Protein Journal, 23, 127–133.CrossRefGoogle Scholar
  13. Kubik, W., Kliś, A., Szewczuk, Z., & Siemion, I. Z. (1984). Proline-rich polypeptide (PRP)—A new peptide immunoregulator and its partial sequences. Peptides, 31, 457–460.Google Scholar
  14. Kubik, A., Szewczuk, Z., Siemion, I. Z., Wieczorek, Z., Spiegel, K., Zimecki, M., Janusz, M., & Lisowski, J. (1988). Configurational requirements of aromatic amino acid residues for the activity of PRP-hexapeptide. Collection Czechoslovak Chemical Communications, 53, 2583–2590.CrossRefGoogle Scholar
  15. Kubis, A., Marcinkowska, E., Janusz, M., & Lisowski, J. (2005) Studies on the mechanism of action of a proline-rich polypeptide complex (PRP): Effect on the stage of cell differentiation. Peptides, 26, 2188–2192.CrossRefGoogle Scholar
  16. Leszek, J., Inglot, A. D., Janusz, M., Lisowski, J., Krukowska, K., & Georgiades, J. A. (1999). Colostrinin: A proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer’s disease. A double-blind, placebo-controlled study. Archivum Immunologiae et Therapiae Experimentalis, 47, 377–385.Google Scholar
  17. Leszek, J., Inglot, A. D., Janusz, M., Byczkiewicz, F., Kiejna, A., Georgiades, J. A., & Lisowski, J. (2002). Colostrinin proline-rich polypeptide complex from ovine colostrum—A long-term study of its efficacy in Alzheimer’s disease. Medical Science Monitor, 8, P193–P196.Google Scholar
  18. Ling, Y., Morgan, K., & Kalsheker, N. (2003). Amyloid precursor protein (APP) and the biology of proteolytic processing: Relevance to Alzheimer’s disease. International Biochemistry and Cell Biology, 35, 1505–1535.CrossRefGoogle Scholar
  19. Lisowski, J., Wieczorek, Z., Janusz, M., & Zimecki, M. (1988). Proline-rich polypeptide (PRP) from ovine colostrum. Bi-directional modulation of binding of peanut agglutinin. Resistance to hydrocortisone, and helper activity in murine thymocytes. Archivum Immunologiae et Therapiae Experimentalis, 36, 381–393.Google Scholar
  20. Popik, P., Bobula, B., Janusz, M., Lisowski, J., & Vetulani, J. (1999). Colostrinin, a polypeptide isolated from early milk, facilitates learning and memory in rats. Pharmacology Biochemistry and Behavior, 64, 183–189.CrossRefGoogle Scholar
  21. Popik, P., Galoch, Z., Janusz, M., Lisowski, J., & Vetulani, J. (2001). Cognitive effects of colostral-Val nonapeptide in aged rats. Behavioural Brain Research, 118, 201–208.CrossRefGoogle Scholar
  22. Schuster, D., Rajendran, A., Wen Hui, S., Nicotera, T., Srikrishnan, T., & Kruzel, M. (2005). Protective effect of Colostrinin on neuroblastoma cell survival is due to reduced aggregation of β-amyloid. Neuropeptides, 39, 419–426.CrossRefGoogle Scholar
  23. Sokal, I., Janusz, M., Miecznikowska, H., Kupryszewski, G., & Lisowski, J. (1998) Effect of colostrinin, an immunomodulatory proline-rich polypeptide from ovine colostrum, on sialidase and β-galactosidase activities in murine thymocytes. Archivum Immunologiae et Therapiae Experimentalis, 46, 193–198.Google Scholar
  24. Starościk, K., Janusz, M., Zimecki, M., Wieczorek, Z., & Lisowski, J. (1983). Immunologically active nonapeptide fragment of a proline-rich polypeptide from ovine colostrum: Amino acid sequence and immunoregulatory properties. Molecular Immunology, 20, 1277–1282.CrossRefGoogle Scholar
  25. Stewart, M. G., & Banks, D. (2006.) Enhancement of long-term memory retention by Colostrinin in one-day-old chicks trained on a weak passive avoidance learning paradigm. Neurobiology of Learning and Memory, 86, 66–71.CrossRefGoogle Scholar
  26. Szewczuk, Z., Kubik, A., Siemion, I. Z., Wieczorek, Z., Spiegel, K., Zimecki, M., & Lisowski, J. (1988). Conformational modification of the PRP-hexapeptide by a direct covalent attachment of aromatic side chain groups. International Journal of Peptide Protein Research, 32, 98–103.CrossRefGoogle Scholar
  27. Szewczuk, Z., Kubik, A., & Gocka, G. (1991). New analogs of the immunoregulatory PRP-pentapeptide. Peptides, 12, 487–492.CrossRefGoogle Scholar
  28. Wieczorek, Z., Zimecki, M., Janusz, M., Starościk, K., & Lisowski, J. (1979). Proline-rich polypeptide from ovine colostrums: Its effect on skin permeability and on the immune response. Immunology, 36, 875–881.Google Scholar
  29. Wieczorek, Z., Zimecki, M., Spiegel, K., Lisowski, J., & Janusz, M. (1989). Differentiation of T cells from immature precursors: Identification of a target cell for a proline-rich polypeptide (PRP). Archivum Immunologiae et Therapiae Experimentalis, 37, 313–322.Google Scholar
  30. Zimecki, M., Janusz, M., Starościk, K., Wieczorek, Z., & Lisowski, J. (1978). Immunological activity of a proline-rich polypeptide from ovine colostrum. Archivum Immunologiae et Therapiae Experimentalis, 26, 23–29.Google Scholar
  31. Zimecki, M., Janusz, M., Starościk, K., Lisowski, J., & Wieczorek, Z. (1982a). Effect of a proline-rich polypeptide on donor cells in graft-versus-host reaction. Immunology, 47, 141–147.Google Scholar
  32. Zimecki, M., Starościk, K., Janusz, M., Lisowski, J., & Wieczorek, Z. (1982b). Effect of PRP on autologous rosette formation in mice. Archivum Immunologiae et Therapiae Experimentalis, 31, 7–13.Google Scholar
  33. Zimecki, M., Starościk, K., Lisowski, J., & Wieczorek, Z. (1983). The inhibitory activity of a proline-rich polypeptide (PRP) on the immune response to polyvinylpyrrolidone (PVP). Archivum Immunologiae et Therapiae Experimentalis, 31, 895–903.Google Scholar
  34. Zimecki, M., Lisowski, J., Hraba, J., Wieczorek, Z., Janusz, M., & Starościk, K. (1984a). The effect of a proline-rich polypeptide (PRP) on the humoral immune response. I. Distinct effect of PRP on the T cell properties of mouse glass-nonadherent (NAT) and glass-adherent (GAT) thymocytes in thymectomized mice. Archivum Immunologiae et Therapiae Experimentalis, 32, 191–195.Google Scholar
  35. Zimecki, M., Lisowski, J., Hraba, T., Wieczorek, Z., Janusz, M., & Starościk, K. (1984b). The effect of a proline-rich polypeptide (PRP) on the humoral immune response. II. PRP induces differentiation of helper cells from glass-nonadherent thymocytes (NAT) and suppressor cells from glass-adherent thymocytes (GAT). Archivum Immunologiae et al., Therapiae Experimentalis, 32, 197–201.Google Scholar
  36. Zimecki, M., Pierce, C. W., Janusz, M., Wieczorek, Z., & Lisowski, J. (1987). Proliferative response of T lymphocytes to a proline-rich polypeptide (PRP): PRP mimics mitogenic activity of IL-1. Archivum Immunologiae et Therapiae Experimentalis, 35, 339–349.Google Scholar
  37. Zimecki, M., Hraba, T., Janusz, M., Lisowski, J., & Wieczorek, Z. (1991). Effect of a proline-rich polypeptide (PRP) on the development of hemolytic anemia and survival of New Zealand Black mice. Archivum Immunologiae et Therapiae Experimentalis, 39, 461–467.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Michal Zimecki
    • 1
  1. 1.The Institute of Immunology and Experimental TherapyPoland

Personalised recommendations