MEMBRANE-FORM TUMOR NECROSIS FACTOR : ANALYSIS AND CLINICAL APPLECATION OF ACTIVATED ALVEOLAR MACROPHAGES

• Project/Area Number: 03670323
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: 内科学一般
• Research Institution: UNIVERSITY OF TOKUSHIMA, SCHOOL OF MAEDICINE
• Principal Investigator: SONE Saburo (1993) THIRD DEPARTMENT OF INTERNAL MEDICINE, UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICINE, 医学部, 助教授 (40145024); 仁井 昌彦 (1991-1992) 徳島大学, 医学部, 講師 (10189227)
• Co-Investigator(Kenkyū-buntansha): HAKU Takashi THIRD DEPARTMENT OF INTERNAL MEDICINE, UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICI, 医学部, 助手 ; NII Akihiko THIRD DEPARTMENT OF INTERNAL MEDICINE, UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICI, 医学部, 講師 (10189227) ; 曽根 三郎 徳島大学, 医学部, 助教授 (40145024)
• Project Period (FY): 1991 – 1993
• Project Status: Completed (Fiscal Year 1993)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
• Keywords: membrane TNF-alpha, alveolar macrophages, cytotoxicity, lung cancer / 肺胞マクロファージ / 細胞障害 / 肺癌 / サイトカイン / 膜型腫瘍壊死因子 / マクロファージ / TNF / インターロイキン-4 / 活性酸素 / マクロファ-ジ / 抗腫瘍活性 / 腫瘍壊死因子 / インタ-ロイキン・4

Research Abstract

The expressions of a membrane form TNF (m-TNF) by human alveolar macrophages (AM) and autologous blood monocytes from healthy donors were examined. Upon lipopolysaccharide (LPS) stimulation, AM produced 26-kDa TNF-alpha on thier cell surface. We designed a bioassay for measuring m-TNF in which macrophages were fixed with paraformaldehyde after stimulation for 18hr, then m-TNF activity was assessed as cytotoxicity of fixed macrophages on L929 cells. on LPS istmulation, AM produced significant amounts of m-TNF earlier than TNF-alpha secretion. Interleukin-4 suppressed both m-TNF producition and TNF-alpha secretion. Although blood monocytes produced small amounts of m-TNF, monocyte-derived macrophages showed enhanced m-TNF after cultivation with GM-CSF for 10 days. as a biological activity, m-TNF on activated monocytes significantly augmented interleukin-6 production by a lung cancer cell line, RERF-LC-OK cells. These findings suggest that m-TNF may play important roles in exhibition of amcrophage functions in situ.

Research Products

• [Publications] A.Nii: "Induction of a 26-kDa membrane-form tumor necrosis factor(TNF)-α in human alveolar macrophages." J Leukoc Biol. 53. 29-36 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Mizuno: "Autonomous expressions of cytokine genes by human lung cancer cells and their paracrine regulation." Jpn J Cancer Res. in press.
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] A.Nii, S.Sone, et al.: "Induction of a 26-kDa membrane-form tumor necrosis factor (TNF)-alpha in human alveolar macrophages." J Leukoc Biol. 53. 29-36 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] "Induction of a 26-kDa membrane-form tumor necrosis factor(TNF)-α in human alveolar macrophages." J Leukoc Biol. 53. 29-36 (1993)
• [Publications] K.Mizuno: "Autonomous expressions of cytokine genes by human lung cancer cells and their paracrine regulation." Jpn J Cancer Res. (in press.).
• [Publications] 仁井 昌彦: "ヒト肺胞マクロファージのモノカイン産生動態とIL・4によるその調節作用" Biotherapy. 5. 441-445 (1991)
• [Publications] Geetha Bhaskaran: "Differential effects of interleukin‐4 on superoxide anion production by humen alveolar macrophages stimulated with lipopolysaccharide and interferon‐γ" Journal of Leukocyte Biology. 52. 218-223 (1992)
• [Publications] Etsuko Orino: "IL-4 up‐ragulates IL-1 receptor antagonist gene expression and its proclucfion in human blood monocyties" Journal of Immanology. 149. 925-931 (1992)
• [Publications] Akihiko Nii: "Induetion of a 26-KDa membrane‐form tumor necrosis factor(TNF)-α in human alveolar macrophages" Journal of Leukocyte Biology. 53. (1993)
• [Publications] Yasuhiko Nishioka: "Downーregulation by Interleukin 4 of activation of human alveolar macrophages to the tumoricidal state." Cancer Research. 51. 5526-5531 (1991)