诱导肺泡巨噬细胞分泌细胞毒因子抑制小鼠黑色素瘤肺转移

INHIBITION OF LUNG METASTASIS OF A MOUSE MELANOMA BY INDUCING RELEASE OF CYTOTOXIC FACTORS FROM ACTIVATED ALVEOLAR MACROPHAGES

以腹腔注射卡介苗或康赛宁，再雾化吸入ｒＩＬ－２，来抑制小鼠黑色素瘤Ｂ１６－ＢＬ６细胞的肺转移。结果表明，小鼠肺转移被显著抑制，抑制率最高达７８．９５％，小鼠生存期最多延长了４８．２０％；腹腔注射Ｎ－单甲基－Ｌ－精氨酸（ＮＭＡ）使抑制作用显著减弱，平均下降了６９．００％。体外实验证明，Ｂ１６－ＢＬ６细胞对ＮＯ的细胞毒作用敏感，对ＴＮＦ不敏感。结果显示，肺转移的抑制作用可能主要是活化的肺泡巨噬细胞分泌的ＮＯ介导的。在活化肺泡巨噬细胞基础上雾化吸入ｒＩＬ－２，不失为治疗肿瘤肺转移的另一途径。

BCG or kanserin was injected ip to systemically activate macrophages in C57BL/6 mice.The activated alveolar macrophages were triggered to release cytotoxic factors by aerosolized rIL 2 inhalation.The results showed that experimental lung metastasis was marked inhibited in the treated mice.The inhibitory rate of metastasis was 78.95% and the surviving time of the treated mice increased by 48.20%.The anti metastatic activity could be markedly abrogated by ip injection of NO synthase inhibitor N G monomethly L arginine,leading to a 69.00% decrease in anti metastatic activity.Experiments in vitro confirmed that B16 BL6 was sensitive to NO mediated cytotoxicity but resistant to TNF.The results indicated that the inhibitory effect on pulmonary metastasis is mainly mediated via NO from activated alveolar macrophages.Inhalation of aerosolized rIL 2 following activation of alveolar macrophages may after all be a novel approach in the treatment of pulmonary metastasis.