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Induced Nitric Oxide From Alveolar Macrophages Inhibits Experimental Pulmonary Metastasis in Mice
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Abstract:
The inhibition of pulmonary metastasis by inhalation of aerosolized recombinant 1L-2 (rIL-2) in BCG-primed mice is reported in this paper . (TA2 x 615) Fl mice were given ip BCG twice in two-week apart.Right after the second BCG injection, MA891 cells, a murine mammary adenocarcinoma of TA2 origin, were injected into the tail vein.Treatment with aerosolized rIL -2 by inhalation was given for 1 hr, 3 times a day and lasted for 14 days. After sacrifice, bronchoalveolar lavage was performed and the lavage fluid was examined for nitric oxide content. The number of tumor nodules on the lung surface was recorded as a measure of the extent of pulmonary metastasis. The results showed that in mice so treated, pulmonary metastasis was very significantly inhibited. When rIL-2 treatment was given in BCG-unprimed mice, inhibition of pulmonary metastasis was also observed albeit to a much lesser extent. Significant inhibition of lung metastasis was associated with significant increase in nitric oxide content in the broncho-alveolar lavage fluid. Moreover, when nitric oxide synthase inhibitor, NG monomethyl-L-arginine (7mg/kg) was given ip shortly before each inhalation of rIL-2, accompanied with a significant reduction of nitric oxide in the lavage fluid, the inhibitory effect of rIL-2 in both BCG-primed and -unprimed mice was almost completely abrogated. Taken together, the results clearly indicate that pulmonary metastasis can be effectively treated by the induction of endogenous release of nitric oxide from activated alveolar macrophages.
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