诱导小鼠肺泡巨噬细胞产生一氧化氮抑制肿瘤实验性肺转移

Induced Nitric Oxide From Alveolar Macrophages Inhibits Experimental Pulmonary Metastasis in Mice

本文报道卡介苗(BCG)致敏小鼠雾化吸入基因重组白细胞介素-2(rIL-2)抑制小鼠乳腺癌实验性肺转移。结果显示,小鼠经治疗后肺表面转移瘤结节数显著减少,肺泡灌洗液一氧化氮(NO)含量显著增高。单独雾化吸入rIL-2对部分种瘤小鼠也有一定的抑瘤作用。用NO合成阻断剂(N-单甲基-L-精氨酸,NMA)能几乎完全阻断rIL-2的抑瘤作用。结果表明,雾化吸入rlL-2加BCG处理是治疗小鼠乳腺癌肺转移的一种有效方法,其机制主要是通过诱导活化肺泡巨噬细胞(Mφ)产生NO发挥抑瘤作用。

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.