ML I binds preferentially to ß-galactosides, ML II to ß-galactosides and N-acetyl-galactosides, whereas ML III recognises N-acetyl-galactosides (Table 1) (Franz, 1989, 1991; Pfüller, 1996). The nomenclature of ML is not uniform. Beside the designation given by our group, ML I, ML II, ML III (Franz et al., 1981; Pfüller, 1996), others termed ML I "viscumin" (Olsnes et al., 1982) or Viscum album agglutinin I (VAA I; Samtleben et al., 1985); in this context, VAA II designates apparently a mixture of ML II/ML III (Samtleben et al., 1985).
The ML are cytotoxic as they induce apoptosis, and stimulate immunocompetent cells to produce a set of cytokines (see Büssing, this book). The toxophoric A chains of the toxic lectins, and especially that of ML, are potent effector molecules for the construction of immunotoxins useful as site-directed immunosuppressive and cytotoxic agents (Tonevitsky et al., 1991; Schütt et al., 1989; Pfüller et al., 1988). Further, especially ML I and ML III are new tools in histochemistry to label immunocompetent cells in lymph nodes and other tissues (Pfüller and Niedobitek, 1998; Schumacher et al., 1994, 1995). In the following paragraphs, the isoform pattern of mistletoe lectins, their isolation, characterisation, structure-function relationship and therapeutically relevant properties will be reviewed referring to Franz (1989, 1991), Pfüller (1996) and Büssing (this book).
The haemagglutinating effect of mistletoe extracts were first described by Krüpe (1956) and by Bird (1954). In 1973, Luther et al (Luther, 1976; Franz et al., 1977) isolated a Viscum lectin by galactose treatment of erythrocytes incubated with a mistletoe extract. In 1981, Franz et al. (1981) were able to separate and characterise three different mistletoe lectins, termed ML I, ML II and ML III. The optimised isolation procedure (Eifler et al., 1993) involves PBS extraction of fresh or air dried plant material, absorption of proteins by cation exchangers, elution of the proteins by salt gradient, affinity chromatography on lactosyl-sepharose 4B, elution of ML II/ML III by PBS, elution of ML I by lactose and separation of ML II and ML III by Fast Protein Liquid Chromatography (FPLC) on Mono S. The main properties of ML are given in Table 2. Figure 1 represents a typical electrophoretic separation pattern of the three isolectin groups (Eifler et al., 1993). Depending on seasonal factors and the host tree, mistletoe contains variable amounts of each isolectin groups with different sugar specificities ranging from galactose (ML I), galactose/galNAc (ML II) to galNAc (ML III), as demonstrated by Surface Plasmon Resonance Studies (Figures 2).
Mistletoes grown on pine trees contain mainly ML III and only minor amounts of ML I, while mistletoes growing on deciduous trees contain mainly ML I (Eifler et al., 1993). Host tree and seasonal dependent lectin pattern of mistletoes are demonstrated in Figure 3. The isolectin composition of ML I seems to be related to host tree and frost impact (Pfüller, 1996; Eifler et al., 1993) according to results on preparative isolation of isoforms with heavy (ML I-2) and light (ML I-1) A chain of ML I (Eifler, Pfüller and Pfüller, in preparation). In general, ML I isolated from mistletoes grown
Was this article helpful?