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 .
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|Buffer||0.01M Phosphate – 0.15M NaCl, pH 7.2-7.4.|
|Activity||Less than 1 μg/ml will agglutinate neuraminidase treated human red blood cells.|