RRC ID 39289
著者 Imaizumi K, Kawabe T, Ichiyama S, Kikutani H, Yagita H, Shimokata K, Hasegawa Y.
タイトル Enhancement of tumoricidal activity of alveolar macrophages via CD40-CD40 ligand interaction.
ジャーナル Am J Physiol
Abstract CD40-CD40 ligand (CD40L) interaction was originally defined as important molecules for the development of humoral immunity. Thereafter, some investigations have focused on its essential roles for the induction of cell-mediated immunity in host defenses. Here we investigated the antitumor activity of murine alveolar macrophages through CD40-CD40L interaction. The CD40L gene was transfected into murine lung cancer cells (3LLSA), and CD40L-expressing clones (3LLSA-CD40L) were established. Stimulation of CD40 molecules on the surface of alveolar macrophages with 3LLSA-CD40L cells induced the production of nitric oxide, tumor necrosis factor-alpha, and interleukin-12 and the tumoricidal activity of alveolar macrophages in the presence of interferon-gamma, which increased the surface expression of CD40 molecules on alveolar macrophages. These findings were not observed when alveolar macrophages were obtained from CD40-deficient mice. On the other hand, interleukin-6 production by alveolar macrophages did not depend on CD40-CD40L interaction. We also established a murine melanoma cell line expressing CD40L (B16 4A5-CD40L) that could induce tumoricidal activity of alveolar macrophages. Furthermore, when spleen cells were cocultivated with 3LLSA-CD40L cells, specific cytotoxic T lymphocytes for wild-type 3LLSA cells could be induced. These results suggest that CD40L gene transfer into tumor cells may induce antitumor immunity in a tumor-bearing host and may offer a new strategy for cancer gene therapy.
巻・号 277(1)
ページ L49-57
公開日 1999-7-1
DOI 10.1152/ajplung.1999.277.1.L49
PMID 10409230
MeSH Animals CD40 Antigens / immunology* CD40 Antigens / metabolism CD40 Ligand Cell Membrane / metabolism Cytotoxicity, Immunologic / physiology* DNA, Complementary / physiology Interferon-gamma / pharmacology Interleukin-12 / biosynthesis Interleukin-6 / biosynthesis Lung Neoplasms / metabolism Lung Neoplasms / pathology Macrophages, Alveolar / drug effects Macrophages, Alveolar / immunology* Macrophages, Alveolar / metabolism Macrophages, Alveolar / physiology* Membrane Glycoproteins / genetics Membrane Glycoproteins / immunology* Membrane Glycoproteins / metabolism Mice Mice, Inbred C57BL Nitric Oxide / biosynthesis T-Lymphocytes, Cytotoxic / physiology Transfection Tumor Cells, Cultured / metabolism Tumor Necrosis Factor-alpha / biosynthesis
IF 3.485
引用数 28
WOS 分野 RESPIRATORY SYSTEM PHYSIOLOGY
リソース情報
ヒト・動物細胞 B16 melanoma 4A5(RCB0557)