Gil J, Alvarez R, Viñuela J E, Ruiz de Morales J G, Bustos A, De la Concha E G, Subiza J L
Department of Immunology, Hospital University San Carlos, Madrid, Spain.
Cancer Res. 1990 Nov 15;50(22):7301-6.
We have shown previously that IgM from Ehrlich tumor (ET)-immunized mice, recognizing ET cell surface carbohydrates, protects control mice to a subsequent tumor challenge. The factors involved in such IgM-mediated protection were unknown, since it was independent of complement activation. Here, we have extended these in vivo studies by means of monoclonal IgM antibodies. Two of them (A10 and E1), strongly recognizing ET cells and with specificity to ET cell surface carbohydrates, were selected. The results show that A10 (but not E1 or unrelated IgM antibodies) is able to protect nonimmunized mice against ET growth. Protection by A10 was also seen by reducing 800-fold the initial dose; however, E1 was unsuccessful whatever the dose used. A10-mediated protection was observed in C3-defective mice (cobra venom factor treated) or in C5-deficient DBA/2, but not in silica-treated animals. Endotoxin removal did not affect the protection afforded by A10 while specific IgM depletion prevented any protective effect. In addition, the relationship between natural antibodies of IgM isotype recognizing ET cell surface carbohydrates and mouse strain resistance to this tumor is established. Similarly, this natural resistance seems to be complement independent but macrophage mediated. Therefore, these results indicate that some IgM molecules recognizing cell surface carbohydrates may participate in in vivo tumor suppression by a macrophage-dependent mechanism.
我们之前已经表明，来自艾氏腹水瘤（ET）免疫小鼠的IgM可识别ET细胞表面碳水化合物，能保护对照小鼠免受后续肿瘤攻击。由于这种IgM介导的保护作用独立于补体激活，因此其中涉及的因素尚不清楚。在此，我们通过单克隆IgM抗体扩展了这些体内研究。挑选出其中两种（A10和E1）能强烈识别ET细胞且对ET细胞表面碳水化合物具有特异性的抗体。结果表明，A10（而非E1或无关的IgM抗体）能够保护未免疫小鼠免受ET生长的影响。将初始剂量降低800倍时也能观察到A10的保护作用；然而，无论使用何种剂量，E1均未成功发挥作用。在C3缺陷小鼠（经眼镜蛇毒因子处理）或C5缺陷的DBA/2小鼠中观察到了A10介导的保护作用，但在经二氧化硅处理的动物中未观察到。去除内毒素并不影响A10提供的保护作用，而特异性IgM耗竭则会阻止任何保护作用。此外，还建立了识别ET细胞表面碳水化合物的IgM同种型天然抗体与小鼠品系对该肿瘤的抗性之间的关系。同样，这种天然抗性似乎不依赖补体，但由巨噬细胞介导。因此，这些结果表明，一些识别细胞表面碳水化合物的IgM分子可能通过巨噬细胞依赖性机制参与体内肿瘤抑制。
