Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP). Cândido Portinari, 200 - Cidade Universitária, Campinas, São Paulo, 13083-871, Brazil.
Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, UNICAMP. Av. Bertrand Russel, Campinas, São Paulo, 13083-865, Brazil.
J Biochem. 2021 Sep 22;170(1):51-68. doi: 10.1093/jb/mvab020.
Immunomodulation has been considered an important approach in the treatment of malignant tumours. However, the modulation of innate immune cells remains an underexplored tool. Studies from our group demonstrated that the Phoneutria nigriventer spider venom (PnV) administration increased the infiltration of macrophage in glioblastoma, in addition to decreasing the tumour size in a preclinical model. The hypothesis that PnV would be modulating the innate immune system led us to the main objective of the present study: to elucidate the effects of PnV and its purified fractions on cultured macrophages. Results showed that PnV and the three fractions activated macrophages differentiated from bone marrow precursors. Further purification generated 23 subfractions named low weight (LW-1 to LW-12) and high weight (HW-1 to HW-11). LW-9 presented the best immunomodulatory effect. Treated cells were more phagocytic, migrated more, showed an activated morphological profile and induced an increased cytotoxic effect of macrophages on tumour cells. However, while M1-controls (LPS) increased IL-10, TNF-alpha and IL-6 release, PnV, fractions and subfractions did not alter any cytokine, with the exception of LW-9 that stimulated IL-10 production. These findings suggest that molecules present in LW-9 have the potential to be used as immunoadjuvants in the treatment of cancer.
免疫调节被认为是治疗恶性肿瘤的重要方法。然而，先天免疫细胞的调节仍然是一个未被充分探索的工具。我们小组的研究表明，Phoneutria nigriventer 蜘蛛毒液（PnV）的给药增加了神经胶质瘤中巨噬细胞的浸润，此外还在临床前模型中减少了肿瘤大小。PnV 会调节先天免疫系统的假设促使我们提出了本研究的主要目标：阐明 PnV 及其纯化部分对培养的巨噬细胞的影响。结果表明，PnV 和三个部分激活了从骨髓前体分化而来的巨噬细胞。进一步的纯化产生了 23 个亚部分，分别命名为低分子量（LW-1 到 LW-12）和高分子量（HW-1 到 HW-11）。LW-9 表现出最佳的免疫调节作用。经处理的细胞具有更强的吞噬作用、迁移能力更强、呈现出激活的形态特征，并诱导巨噬细胞对肿瘤细胞的细胞毒性作用增强。然而，虽然 M1 对照（LPS）增加了 IL-10、TNF-alpha 和 IL-6 的释放，但 PnV、部分和亚部分没有改变任何细胞因子，除了 LW-9 刺激了 IL-10 的产生。这些发现表明，LW-9 中存在的分子有可能被用作癌症治疗中的免疫佐剂。
