Thomassen M J, Barna B P, Wiedemann H P, Ahmad M
Department of Pulmonary Disease, Cleveland Clinic Foundation, Ohio 44195-5038.
J Biol Response Mod. 1990 Feb;9(1):87-91.
Recombinant macrophage colony-stimulating factor (M-CSF) is a hemopoietic growth factor capable of modulating activities of both immature and mature monocytes. The effect of M-CSF on tumoricidal activity of alveolar macrophages and monocytes from nonsmoking normal volunteers was compared using [3H]thymidine-labeled human tumor cells (SK-MEL-28, melanoma) as targets. A dose-response study (500-5,000 U/ml) of recombinant M-CSF indicated that both alveolar macrophages and blood monocytes demonstrated peak cytotoxicity at 1,000 U/ml. Maximal activity occurred 72-96 h after exposure to 1,000 U/ml of M-CSF. To investigate the mechanisms involved in this cytotoxicity, tumor necrosis factor-alpha (TNF) and interleukin-1-beta (IL-1) were measured in supernatant fluids of 24 h M-CSF-treated cells. No significant increase in either cytokine was detected after M-CSF treatment of alveolar macrophages or monocytes. Superoxide anion production of alveolar macrophages was not enhanced by M-CSF. These data suggest that alveolar macrophages tumoricidal activity is induced by M-CSF and is not dependent on oxidative metabolism or secreted forms of IL-1 or TNF.
重组巨噬细胞集落刺激因子（M-CSF）是一种造血生长因子，能够调节未成熟和成熟单核细胞的活性。以[3H]胸腺嘧啶核苷标记的人肿瘤细胞（SK-MEL-28，黑色素瘤）为靶标，比较了M-CSF对来自不吸烟正常志愿者的肺泡巨噬细胞和单核细胞杀肿瘤活性的影响。重组M-CSF的剂量反应研究（500-5000 U/ml）表明，肺泡巨噬细胞和血液单核细胞在1000 U/ml时均表现出最大细胞毒性。最大活性在暴露于1000 U/ml M-CSF后72-96小时出现。为了研究这种细胞毒性的机制，在M-CSF处理24小时的细胞的上清液中测量了肿瘤坏死因子-α（TNF）和白细胞介素-1-β（IL-1）。M-CSF处理肺泡巨噬细胞或单核细胞后，未检测到两种细胞因子有显著增加。M-CSF未增强肺泡巨噬细胞的超氧阴离子产生。这些数据表明，肺泡巨噬细胞的杀肿瘤活性由M-CSF诱导，且不依赖于氧化代谢或IL-1或TNF的分泌形式。
