Immunomodulatory Effects by Mistletoe Lectin

Abstract

It is well accepted that the important effectors of natural resistance against tumor, such as natural killer (NK) cells and macrophages share some similarities in that they do not require prior sensitization (5,11), can lyse across HLA or H2 barriers (5,11,13) and can kill a wide variety of targets. In addition it has been shown that many types of monosaccharide can inhibit effectively both NK cell activity and spontaneous macrophage cytotoxicity towards tumor cell lines (3,8,9,14,17). To account for these findings it has been proposed that both NK cells (9,14,16) and macrophages (8,17) bear lectin-like receptors reactive with carbohydrate determinants on target cells, which are probably part of complex glycoproteins or alycolipids of the membrane (14). It has been shown that the influence of host NK cells on metastatic spread of tumor cells may depend in part on the density of specific oliaosaccharide structures on the tumor cell surface (1). Although in most cases the biochemical nature of the involvement of such saccharides remains uncharacterized at the moment (3), growing interest has been focussed on the findings of several investigators that some lectins, originated from plant or animals, were able to induce tumorspecific cytotoxicity of macrophages (7,12) and interferon (IFN)-γ production of human peripheral T cells (15). In addition treatment of tumor-bearing mice with such lectins have a significant antitumor effect (6). Several studies in accordance with our experience suggest that mistletoe lectins (ML) may be of importance in the immunomodulation observed following the therapy with mistletoe extracts (2, 4, 10). Three types of 200 ML were found: ML I, ML II and ML III (2). The most important D-galactose specific ML I (MW = 115 000) consists of two A chains (MW = 34 000) and two carbohydrate binding B chains (MW = 29 000). In the present study we have investigated whether ML I and its subunits purified from mistletoe extracts (Iscador) may exhibit immunomodulatory effects.