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

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