Lipopolysaccharide-activated alveolar macrophages having cytotoxicity toward lung tumor cells through cell-to-cell binding-dependent mechanism

Anticancer Res. 2010 Aug;30(8):3159-65.


Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Cell Fusion*
  • Cell Line, Tumor
  • Coculture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Interleukin-1 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Macrophage Activation / drug effects*
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / immunology
  • Nitric Oxide / biosynthesis
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-1
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide