Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Anticancer Res. 2010 Aug;30(8):3159-65.
In lung tumor biotherapy, local macrophages such as alveolar macrophages and tumor-associated macrophages (TAMs) which normally exist in contact with tumor cells are thought to be hopeful target. It is advantageous to clarify the potential for and mechanism by which lung tumor cells are killed by the neighboring macrophages in order to establish new lung cancer therapy using a drug delivery system to lung tissue.
A549, a human lung adenocarcinoma cell line, and Lewis lung carcinoma LLC1, a mouse lung cancer cell line, were co-cultured with NR8383, a rat alveolar macrophage cell line, and AMJ2-C11, a mouse alveolar macrophage cell line, at a ratio of 1:10 and 1:5, respectively. Macrophages were activated with lipopolysaccharide (LPS) and cytotoxicity toward tumor cells was evaluated by a dye-uptake method and (3)H-thymidine release assay, respectively. Nitric oxide (NO) production was estimated by Griess assay, and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured by ELISA.
Significant macrophage cell aggregation and cytotoxicity against A549 cells and LLC1 cells was observed with NR8383 cells and AMJ2-C11 cells in the presence of LPS. A high concentration of NO and TNF-α were detected in the supernatant of co-culture medium with LPS. Inhibition of cell-to-cell contact restored A549 cell growth.
The LPS-activated alveolar macrophages demonstrated an increased cell-to-cell contact with lung tumor cells and inducing cytotoxicity with production of NO and cytokines TNF-α and IL-1β. These results suggest that moderate activation of local macrophages in lung (alveolar macrophages and TAMs) is thought to be a hopeful means of establishing new immunotherapy for lung cancer.
在肺部肿瘤的生物治疗中，局部巨噬细胞如肺泡巨噬细胞和肿瘤相关巨噬细胞（TAMs）通常与肿瘤细胞接触，被认为是有希望的靶点。为了利用药物输送系统向肺部组织建立新的肺癌治疗方法，阐明肺肿瘤细胞被邻近巨噬细胞杀死的潜力和机制是有利的。
将人肺腺癌 A549 细胞系和小鼠肺癌 LLC1 细胞系分别与 NR8383 大鼠肺泡巨噬细胞系和 AMJ2-C11 小鼠肺泡巨噬细胞系以 1:10 和 1:5 的比例共培养，巨噬细胞用脂多糖（LPS）激活，并通过染料摄取法和（3）H-胸苷释放试验分别评估对肿瘤细胞的细胞毒性。通过 Griess 法测定一氧化氮（NO）的产生，通过 ELISA 测定肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β。
用 LPS 处理时，NR8383 细胞和 AMJ2-C11 细胞与 A549 细胞和 LLC1 细胞共培养时观察到明显的巨噬细胞细胞聚集和细胞毒性。LPS 存在时，共培养培养基上清液中检测到高浓度的 NO 和 TNF-α。细胞间接触抑制恢复了 A549 细胞的生长。
LPS 激活的肺泡巨噬细胞与肺肿瘤细胞的细胞间接触增加，并通过产生 NO 和细胞因子 TNF-α和 IL-1β诱导细胞毒性。这些结果表明，适度激活肺部（肺泡巨噬细胞和 TAMs）的局部巨噬细胞被认为是建立新的肺癌免疫治疗的有希望的手段。
