| First Author | Imaizumi K | Year | 1999 |
| Journal | Am J Physiol | Volume | 277 |
| Issue | 1 Pt 1 | Pages | L49-57 |
| PubMed ID | 10409230 | Mgi Jnum | J:56448 |
| Mgi Id | MGI:1340969 | Doi | 10.1152/ajplung.1999.277.1.L49 |
| Citation | Imaizumi K, et al. (1999) Enhancement of tumoricidal activity of alveolar macrophages via CD40-CD40 ligand interaction. Am J Physiol 277(1 Pt 1):L49-57 |
| abstractText | 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. |
