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) |