Brault M S, Kurt R A
J Biomed Biotechnol. 2005;2005(1):37-43. doi: 10.1155/JBB.2005.37.
Monocyte chemoattractant protein-1 (MCP-1, CCL2) is produced by many different types of cells. In the current investigation, the effect of tumor-derived CCL2 on macrophages was evaluated to determine the extent to which this chemokine influenced the innate immune response to cancer. To do this, we used the 4T1 murine mammary carcinoma cell line that constitutively expresses CCL2 and generated 4T1 expressing an antisense CCL2 transcript. The antisense-CCL2-expressing 4T1 produced no detectable CCL2. Macrophages from female BALB/c mice were exposed to supernatants from these tumor cells. The results showed that tumor-derived CCL2 was capable of modulating cytokine gene expression but not protein production in resting, activated, and tumor-associated macrophages. In addition, tumor-derived CCL2 did not affect phagocytic activity, nitric oxide production, or cytolytic activity of the macrophages. Overall, these data suggest that tumor-derived CCL2 does not directly influence macrophage-mediated antitumor activity.
单核细胞趋化蛋白-1(MCP-1,CCL2)由多种不同类型的细胞产生。在当前的研究中,评估了肿瘤来源的CCL2对巨噬细胞的影响,以确定这种趋化因子在多大程度上影响了对癌症的先天性免疫反应。为此,我们使用了组成型表达CCL2的4T1小鼠乳腺癌细胞系,并生成了表达反义CCL2转录本的4T1细胞。表达反义CCL2的4T1细胞不产生可检测到的CCL2。将雌性BALB/c小鼠的巨噬细胞暴露于这些肿瘤细胞的上清液中。结果表明,肿瘤来源的CCL2能够调节静息、活化和肿瘤相关巨噬细胞中的细胞因子基因表达,但不影响蛋白质产生。此外,肿瘤来源的CCL2不影响巨噬细胞的吞噬活性、一氧化氮产生或细胞溶解活性。总体而言,这些数据表明肿瘤来源的CCL2不会直接影响巨噬细胞介导的抗肿瘤活性。