title: Innate-immune therapy for lung carcinoma based on tissue-macrophage activation with lipopolysaccharide.
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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Health Sciences, Tokushima Bunri University, Nishihama, Yamashiro-cho, Tokushima-shi, 770-8514, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Hino
authors.forename: Chie
authors.initials: C
authors.lastname: Kohchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishizawa
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kazue
authors.initials: K
authors.lastname: Nakata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inagawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hori
authors.forename: Kimiko
authors.initials: K
authors.lastname: Makino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terada
authors.forename: Gen-Ichiro
authors.initials: G
authors.lastname: Soma
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000818:Animals; D016923:Cell Death / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D018920:Coculture Techniques; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats
chemical_list: D008070:Lipopolysaccharides; D009569:Nitric Oxide