Toxicity of lectin extracted from Korean mistletoe (Viscum album coloratum) in chicks and its immunoadjuvant activity on Newcastle disease virus vaccines

한국산 겨우살이(Viscum album coloratum)로부터 추출된 lectin의 닭에 대한 독성 및 뉴캐슬병 백신의 특이면역 증강 효과

  • Yeo, Sang-Geon (College of Veterinary Medicine, Kyungpook National University)
  • Accepted : 2006.09.08
  • Published : 2006.09.30

Abstract

In order to search the availability of the lectin extracted from Korean mistletoe(Viscum album coloratum) as an adjuvant for the avian vaccines, attempts were made to determine toxicity of the lectin in chicks and its immunostimulating activity on the inactivated vaccines against Newcastle disease virus(NDV). For the determination of toxicity, the lectin was injected into the thigh muscle of SPF chicks(Charles River) of 1-week-old and observed hematologically and pathologically. For the determination of immunostimulating effects, lectin-adjuvanted, inactivated NDV vaccines were injected into the thigh muscle of SPF chicks in the same age group. Sera of the chicks were examined for the hemagglutination-inhibition(HI) antibodies induced, their HI titers and reaction to the NDV antigens. The data were further compared with those from aluminum hydroxide [$Al(OH)_3$]-adjuvanted vaccines and vaccines without adjuvant, and the results are as follows. There were no significant changes observed in the values of RBC, WBC, Hb, PCV, MCV, MCH, MCHC, AST, ALT, BUN, creatinine and total proteins in the chicks administered with lectin of 1.1, 2.2 and $22.2{\mu}g/kg$ body weight, which means the lectin has no effects on blood values and functions of liver and kidney. In histopathologic observation, no lesions were observed in the brain, heart, liver, lung, spleen, kidney, thymus and bursa of Fabricius of the chicks administered with lectin of 1.1, 2.2 and $22.2{\mu}g/kg$ body weight. There were inflammatory lesions, such as congestion, hemorrhage, edema, infiltration of macrophages and coagulation necrosis observed in the thigh muscle of chicks administered with lectin of $22.2{\mu}g/kg$ body weight, whereas no changes were observed in 1.1 and $22.2{\mu}g/kg$ lectin administered chicks. In chicks immunized with lectin($4.4{\mu}g/kg$ of body weight)-adjuvanted B1, LaSota and Ulster 2C vaccines, HI titers in reciprocal values for $log_2$ were 1.8-2.2 at 1 week after vaccination, which was similar with those of 1.5-2.9 by $Al(OH)_3$-adjuvanted vaccines. The HI titers by the lectin-adjuvanted vaccines reached to 3.9-5.3 at 4 weeks, whereas those by the $Al(OH)_3$-adjuvanted vaccines were more high as 7.3-9.3. Meanwhile, the immunostimulating effects of the lectin were recognized while compared to the HI titers with 2.4-3.7 in chicks immunized with vaccines without adjuvants at 4 weeks after vaccination. The chicks immunized with lectin-adjuvanted vaccines were enough to resist challenges by Kyojeongwon strain, a very virulent NDV at 4 weeks after vaccination as well as chicks immunized with $Al(OH)_3$-adjuvanted vaccines. The HI titers by the lectin-adjuvanted vaccines reached to high level as 8.7-10.3 as those with 8.2-9.6 by the $Al(OH)_3$-adjuvanted vaccines at 6 weeks after vaccination, which may be the booster effects by the challenge virus. Antibodies specific to the HN and F antigens of NDV were observed in the sera of both chicks immunized with lectin-adjuvanted vaccines and $Al(OH)_3$-adjuvanted vaccines.

Keywords

References

  1. 강태봉, 윤택준, 김종배, 송성규, 이관희, 곽진환. 한국산 겨우살이(Viscum album coloratum)로부터 정제된 렉틴 성분 KML-IIU의 예비 독성 및 일반 약리시험. 약학회지, 2001, 45, 251-257
  2. 신민교. 원색임상본초학. pp. 237-238, 영림출판사, 서울, 1988
  3. 윤택준, 유영춘, 강태봉, 도명술, 서병선, Azuma I, 김종배. 한국산 겨우살이 추출물(Viscum album coloratum; KM-110)의 면역학적 활성. 대한면역학회지, 1997, 19 571-581
  4. 윤택준, 유영춘, 홍은경, 조영호, 이석원, Auma I, 유보림, 김종배. 마우스 macrophage의 IL-1 및 $TNF-{\alpha}$의 분비유도에 있어서 한국산 겨우살이 추출물이 미치는 영향. 생약학회지, 1994, 25, 132-139
  5. Beard CW. Serologic procedures. In: Purachase HG, Arp LH, Domermuth CH, Pearson JE. (eds). A laboratory manual for the isolation and identification of avian pathogens. 3rd ed. pp. 192-194, Kendall/Hunt Publishing Company, Dubuque, 1990
  6. Becker H. Botany of European mistletoe(Viscum album L.). Oncology, 1986, 43, 2-7 https://doi.org/10.1159/000226413
  7. Bloksma N, Dijk HV, Korst P, Willer JM. Cellular and humoral adjuvant activity of Mistletoe extract. Immunobiol, 1979, 156, 309-319
  8. Bloksma N, Schmiermann P, de Reuver M, Dijk HV, Willer JM. Stimulation of humoral and cellular immunity by Viscum preparations. J Med Plant Res, 1982, 46, 2-8
  9. Fisher S, Scheffler A, Kabelitz D. Stimulation of the specific immune system by mistletoe extracts. Anticancer Drugs, 1997, 8, 33-37
  10. Hajto T, Hostanska K, Gabius HJ. Modulatory potency of the b-galactoside-specific lectin from mistletoe extract(Iscador) on the host defence system in vitro in rabbits and patients. Cancer Res, 1989, 49, 4803-4808
  11. arlow H, Lane D. Antibodies: A laboratory manual. pp. 471-510, Cold Spring Harbor Laboratory, New York, 1988
  12. Holtskog R, Sand K, Olsnes S. Characterization of a toxin lectin in Iscador, a mistletoe preparation with alleged cancerostatic properties. Oncology, 1988, 45, 172-179 https://doi.org/10.1159/000226557
  13. Kelleher CJ, Halvorson DA, Newman JA. An evaluation of Newcastle disease virus spray vaccination programs of market turkeys. Avian Dis, 1987, 31, 431-437, 1987 https://doi.org/10.2307/1590720
  14. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 1970, 227, 680-685 https://doi.org/10.1038/227680a0
  15. Lavelle EC, Grant G, Pusztai A, Pfuller U, O'Hagan DT. Mucosal immunogenicity of plant lectins in mice. Immunol, 2000, 99, 30-37 https://doi.org/10.1046/j.1365-2567.2000.00932.x
  16. Lavelle EC, Grant G, Pusztai A, Pfuller U, O'Hagan DT. The identification of plant lectins with mucosal adjuvant activity. Immunol, 2001, 102, 77-86 https://doi.org/10.1046/j.1365-2567.2001.01157.x
  17. Meulemans G, Gonze M, Carlier MC, Petit P, Burny A, Long L. Protective effects of HN and F glucoprotein-specific monmoclonal antibodies on experimental Newcastle disease. Avian Pathol, 1986, 15, 761-786 https://doi.org/10.1080/03079458608436338
  18. Morrison T, Hinshaw V, Sheerar M, Cooley AJ, Brown D, McQuain C, McGines L. Retrovirus expressed hemagglutinin-neuraminidase protein protects chickens from Newcastle disease virus induced disease. Microbial Pathogen, 1990, 9, 387-396 https://doi.org/10.1016/0882-4010(90)90057-W
  19. Nishino Y, Niikura M, Suwa T, Onuma M, Gotoh B, Nagai Y, Mikami T. Analysis of the protective effect of the hemagglutinin-neuraminidase protein in Newcastle disease virus infection. J Gen Virol, 1991, 72, 1187-1190 https://doi.org/10.1099/0022-1317-72-5-1187
  20. Payment P, Trudel M. Methods and Techniques in Virology. pp. 33, Marcel Dekker, New York, 1983
  21. Rentea R, Lyon E, Hunter R. Biologic properties of Iscador: A Viscum album preparation. I. Hyperplasia of the thymic cortex and accelerated regeneration of hematopoietic cells following X-irradiation. Lab Invest, 1981, 44, 43-48
  22. Ribereau-Gayon G, Dumont S, Muller C, Jung ML, Poindron P, Anton R. Mistletoe lectins I, II and III induce the production of cytokines by cultured human monocytes. Cancer Letters, 1996, 109, 33-38 https://doi.org/10.1016/S0304-3835(96)04401-1
  23. Tizard IR. Veterinary Immunology: An introduction. 7th ed. pp. 256-258, Saunders, China, 2004
  24. Yoon TJ, Yoo YC, Kang TB, Baek YJ, Huh CS, Song SK, Lee KH, Azuma I, Kim JR. Prophylactic effect of Korean mistletoe(Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity. Inter J Immunopharm, 1998, 20, 163-172 https://doi.org/10.1016/S0192-0561(98)00024-1