Das P C, Roberts J D, White S L, Olden K
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Oncol Res. 1995;7(9):425-33.
The induction of macrophage tumoricidal activity by swainsonine (8a beta-indolizidine-1 alpha, 2 alpha, 8 beta-triol), an indolizidine alkaloid, has been implicated as possibly an important immune effector mechanism involved in the suppression of tumor growth and metastasis in vital organs such as the lung, liver and spleen (Olden, K. et al. The potential importance of swainsonine in therapy for cancers and immunology. Pharmacol. Ther. 50:285-290; 1991). The present study further explores this possibility by determining whether resident tissue-specific macrophages of several mouse strains can be rendered tumoricidal by systemic administration of swainsonine. We found that systemically administered swainsonine could increase the tumoricidal activity of both alveolar (lung) and splenic macrophages. The activity was enhanced as much as 3- to 4-fold over that obtained with macrophages from organs of control animals and was both dose- and time-dependent. The level and extent of activation by swainsonine was comparable to that achieved with traditional macrophage-activating agents, such as lipopolysaccharide and interferon-gamma. The fact that swainsonine activated highly purified (> 95%) cultures of macrophages from the various sources suggests a direct mechanism of activation. Furthermore, the in vivo activation of macrophages in immune-compromised animals (SCID and nude) lends credence to this suggestion. These findings provide a plausible explanation for the observations that systemically administered swainsonine inhibits organ colonization of metastatic cells and growth of SC tumor xenografts, whereas the growth of tumor cells is not inhibited by swainsonine in culture.
苦马豆素（8aβ-吲哚里西啶-1α，2α，8β-三醇）是一种吲哚里西啶生物碱，它诱导巨噬细胞的杀肿瘤活性可能是参与抑制肺、肝和脾等重要器官肿瘤生长和转移的一种重要免疫效应机制（奥尔登，K.等人。苦马豆素在癌症治疗和免疫学中的潜在重要性。药理学与治疗学。50:285 - 290；1991年）。本研究通过确定全身给予苦马豆素是否能使几种小鼠品系的组织特异性驻留巨噬细胞具有杀肿瘤活性，进一步探讨了这种可能性。我们发现，全身给予苦马豆素可增强肺泡（肺）巨噬细胞和脾巨噬细胞的杀肿瘤活性。与对照动物器官的巨噬细胞相比，该活性增强了3至4倍，且具有剂量和时间依赖性。苦马豆素激活的水平和程度与传统巨噬细胞激活剂（如脂多糖和干扰素-γ）所达到的相当。苦马豆素能激活来自各种来源的高度纯化（>95%）巨噬细胞培养物，这一事实提示了一种直接的激活机制。此外，免疫受损动物（SCID和裸鼠）体内巨噬细胞的激活也支持了这一观点。这些发现为以下观察结果提供了一个合理的解释：全身给予苦马豆素可抑制转移细胞在器官中的定植和SC肿瘤异种移植物的生长，而在培养中苦马豆素并不抑制肿瘤细胞的生长。
