Viscum album

About the Lectin

A group of three similar cytotoxic lectins are found in leaves of the European mistletoe, Viscum album 1,2 . An American mistletoe, Phoradendron californicum, contains a similar toxic lectin 3 . These lectins are type II ribosome-inactivating proteins, similar in structure to ricin, i.e. containing a toxic subunit (A subunit) and a carbohydrate-binding subunit (B subunit) 4,5 . The A subunit of one of the mistletoe lectins (VAA-I) has been sequenced and is highly homologous to the A subunit of ricin 6 ; N-terminal sequences of the three mistletoe lectins are identical 7 . The B subunit of VAA-I has also been partially sequenced; it has ragged N-termini, and overall homology to the B subunit of ricin D and E 8 . The predominant lectin, VAA-I (also designated ML-I or viscumin) is a galactose-specific lectin, which binds both α- and β-galactosides, but with different affinities that depend on the extended structure 9-12 . The lectin also appears to have affinity for sialic acid in some structures 13 . A minor component, ML-II, is considered to be Gal/GalNAc specific, whereas the third, moderately prevalent lectin, ML-III or VAA-II, is GalNAc specific 14 . The relative amounts of the three lectins in a crude lectin preparation depends on the host tree8 and on the season of year 15 . VAA-I and II have been shown to impart frost tolerance to the leaves, and their levels increase during cold seasons 15 . The lectins are active components in the crude mistletoe preparations (VAL) that have been used in some regions as an adjuvant in non-traditional cancer therapy. At subtoxic concentrations, they have immunodulatory properties. They induce mRNA expression and enhance secretion of proimflammatory cytokines in cultures of human peripheral blood monocytes 16 , and in animal studies, VAA-I has been shown to stimulate natural killer cells and granulocytes 17 . These immuno-modulatory effects are attributed to the carbohydrate-binding B subunit 16 . At higher levels, the lectins are cytotoxic, leading to programmed (apoptotic) cell death, as characterized by fragmentation and loss of DNA 18,19 . At still higher concentrations, cell death is by necrosis without DNA fragmentation 19 . The A subunit is sufficient to cause cell death in some cell lines, but the presence of the B subunit provides the optimum cytotoxicity, presumably by binding to cell surface carbohydrate receptors, and promoting the entry of the toxic subunit into the cell.

An unrelated chitin-binding lectin homologous with the hevein domains of other chitin-binding lectins and chitinases, has been isolated from mistletoe 20 .

REFERENCES

  1. Samuelsson, G. (1973) Syst. Zool. 22 : 566-569.
  2. Luther, P., et al. (1977) Acta. Biol. Med. Ger. 36 : 119-125.
  3. Endo, Y., et al. (1989) FEBS Lett. 248 : 115-118.
  4. Olsnes, S., et al. (1982) J. Biol. Chem. 257 : 13263-13270.
  5. Franz, H., et al. (1982) Acta Biol. Med. Ger. 41 : K16-K19.
  6. Huguet Soler, M., et al. (1996) FEBS Lett. 399 : 153-157.
  7. Dietrich, J.B., et al. (1992) Anti-Cancer Drugs 3 : 507-511.
  8. Gabius, H.J., et al. (1992) Anticancer Res. 12 : 669-675.
  9. Lee, R.T., et al. (1992) J. Biol. Chem. 267 : 23722-23727.
  10. Lee, R.T., et al. (1994) Carbohyd. Res. 254 : 269-276.
  11. Debray, H., et al. (1994) Glycoconj. J. 11 : 550-557.
  12. Galanina, O.E., et al. (1997) J. Mol. Recog. 10 : 139-147.
  13. Wu, A.M., et al. (1995) Biochem. Biophys. Res. Comm. 214 : 396-402.
  14. Van Damme, E.J.M., et al. (1998) Handbook of Plant Lectins : Properties and Biomedical Applications. pp. 417-421 Wiley.
  15. Hincha, D.K., et al. (1997) Planta 203 : 140-144.
  16. Haijto, T., et al. (1990) Cancer Res. 50 : 3322-3326.
  17. Haijto, T., et al. (1989) Cancer Res. 49 : 4803-4808.
  18. Bussing, A., et al. (1996) Cancer Lett. 99 : 59-72.
  19. Hostanska, K., et al. (1997) Natural Immunity 15 : 295-311.
  20. Peumans, W.J., et al. (1996) FEBS Lett. 396 : 261-265.

Product Characteristics

Buffer 0.01M Phosphate – 0.15M NaCl, pH 7.2-7.4.
Blood Group Non-specific.
Activity Less than 1 μg/ml will agglutinate neuraminidase treated human red blood cells.
Inhibitory Carbohydrate β-D-galactose.