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


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.


CONCLUSIONS
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.
Taniguchi
Hiroaki
H
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Shimada
Yasuteru
Y
Sawachi
Keiichi
K
Hirota
Keiji
K
Inagawa
Hiroyuki
H
Kohchi
Chie
C
Soma
Gen-Ichiro
G
Makino
Kimiko
K
Terada
Hiroshi
H
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002459:Cell Fusion; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide