Hajto T, Hostanska K, Gabius H J
Laboratory of Immunology, Lucas Clinic, Arlesheim, Switzerland.
Cancer Res. 1989 Sep 1;49(17):4803-8.
Proprietary extract of mistletoe (Iscador) that has federal approval for clinical application can exhibit immunomodulatory capacity. However, the nature of this responsible substance has still remained elusive. To validate the hypothesis that specific lectin-carbohydrate interactions at least participate in eliciting immunomodulation, the modulatory efficiency of the major beta-galactoside-specific mistletoe lectin (ML I) from the clinically applied extract on selected immunological parameters was monitored "in vivo" in rabbits. Injections of nontoxic doses of the purified lectin or even only of its carbohydrate-binding subunit (0.25-1.0 ng/kg) into rabbits yielded significant increases in natural killer cytotoxicity, frequency of large granular lymphocytes, and phagocytic activity of granulocytes. In the clinically relevant situation, changes in these parameters were also determined in cancer patients after extract (Iscador) injection s.c. as well as i.v., emphasizing the potential relevance of the lectin. Comparative analyses of the changes in the selected parameters following injection of extract with normal lectin content as well as of extract, selectively depleted of lectin, into healthy volunteers corroborated this inference. Lectin depletion by affinity chromatography was highly specific and did not affect any other substance in the extract. Remarkably, contamination by endotoxin has been rigorously excluded in each applied specimen. These results encourage detailed elucidation of lectin action on various parts of the tumor defense system "in vitro" with the long range goal of achieving progress in the treatment of cancer through immunological strategies, exploring selective mediatory lectin-carbohydrate interactions.
已获得联邦临床应用批准的槲寄生专有提取物（Iscador）具有免疫调节能力。然而，这种起作用物质的性质仍然难以捉摸。为了验证特定凝集素 - 碳水化合物相互作用至少参与引发免疫调节的假设，在兔子体内监测了临床应用提取物中主要的β - 半乳糖苷特异性槲寄生凝集素（ML I）对选定免疫参数的调节效率。向兔子注射无毒剂量的纯化凝集素或甚至仅其碳水化合物结合亚基（0.25 - 1.0 ng/kg）会使自然杀伤细胞毒性、大颗粒淋巴细胞频率和粒细胞吞噬活性显著增加。在临床相关情况下，癌症患者皮下和静脉注射提取物（Iscador）后，也测定了这些参数的变化，强调了凝集素的潜在相关性。对正常凝集素含量提取物以及选择性去除凝集素的提取物注射后选定参数变化的比较分析证实了这一推断。通过亲和色谱法去除凝集素具有高度特异性，且不影响提取物中的任何其他物质。值得注意的是，每个应用样本都严格排除了内毒素污染。这些结果鼓励在体外详细阐明凝集素对肿瘤防御系统各个部分的作用，其长期目标是通过免疫策略在癌症治疗中取得进展，探索选择性介导的凝集素 - 碳水化合物相互作用。
