Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes.
We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.
D000230:Adenocarcinoma / Q000276:immunology* / Q000556:secondary; D000818:Animals; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008175:Lung Neoplasms / Q000556:secondary*; D008262:Macrophage Activation; D051381:Rats; D011918:Rats, Inbred SHR; D013601:T-Lymphocytes / Q000276:immunology*