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Innate-immune therapy for lung carcinoma based on tissue-macrophage activation with lipopolysaccharide.
- Source :
-
Anticancer research [Anticancer Res] 2005 Nov-Dec; Vol. 25 (6A), pp. 3747-54. - Publication Year :
- 2005
-
Abstract
- Background: Over the last decade, tumor-specific antigens have been discovered, but so far it has not been possible to use them as part of an effective acquired immunotherapy. This failure may be due to the fact that the expression of the MHC class 1 is low and in lung cancer cells is heterogeneous. Therefore, it may be advantageous to develop techniques that activate the antitumor mechanism of the innate immune system. An experimental model was developed for testing lung cancer therapies that are based on the stimulation of macrophages, which then activate innate immunity.<br />Materials and Methods: A549, a human lung adenocarcinoma cell line, was co-cultured with a rat macrophage cell line (NR8383), or a human macrophage cell line (THP 1) at the ratios of 1:1 or 1:5. The experiments were performed with lipopolysaccharide (LPS) or in its absence. The cytotoxicity rate to A549 cells was estimated over time using a dye-uptake method and the amount of lactate dehydrogenase released was measured. The amount of nitric oxide (NO) induced in the medium was assayed, because it may be a candidate as a useful cytotoxic factor.<br />Results: High cytotoxicity was observed to A549 cells when co-cultured with NR8383 cells in the presence of LPS. This effect was not observed in the absence of LPS. Similar results, although to a lesser extent, were observed when A549 cells were co-cultured with THP-1 cells. A high concentration of NO was measured in the co-culture medium of A549 cells and NR8383 cells when LPS was present.<br />Conclusion: The induction of cell death in lung cancer cells occurred after contact with macrophages that had been activated by LPS. The NO that was produced by macrophages in response to LPS was responsible for some of this effect.
- Subjects :
- Adenocarcinoma immunology
Animals
Cell Death immunology
Cell Survival immunology
Coculture Techniques
Humans
Lung Neoplasms immunology
Macrophage Activation drug effects
Macrophages cytology
Macrophages metabolism
Macrophages, Alveolar cytology
Macrophages, Alveolar immunology
Macrophages, Alveolar metabolism
Monocytes cytology
Monocytes immunology
Nitric Oxide biosynthesis
Rats
Adenocarcinoma therapy
Immunotherapy methods
Lipopolysaccharides pharmacology
Lung Neoplasms therapy
Macrophage Activation immunology
Macrophages immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0250-7005
- Volume :
- 25
- Issue :
- 6A
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 16302735