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集落刺激因子对小鼠巨噬细胞的作用。抗肿瘤活性的诱导。

Effect of colony stimulating factor on murine macrophages. Induction of antitumor activity.

作者信息

Wing E J, Waheed A, Shadduck R K, Nagle L S, Stephenson K

出版信息

J Clin Invest. 1982 Feb;69(2):270-6. doi: 10.1172/jci110449.

Abstract

Colony stimulating factor (CSF) was assessed for its capacity to stimulate antitumor activity in macrophages. Murine peritoneal macrophages incubated with CSF for 48 h inhibited [3H[thymidine (TdR) incorporation by P815 tumor cells to approximately 20% of control values. Inhibition of CSF-stimulated macrophages was significantly greater than inhibition by unstimulated macrophages (P less than 0.001). CSF had little direct effect on the proliferation of either tumor cells or macrophages alone, indicating that the antitumor activity of CSF was mediated by macrophages. it is unlikely that impurities in the CSF preparations were responsible for the effect since CSF that had been purified to homogeneity was as active as crude preparations. Furthermore the activity of CSF on macrophages was blocked by addition of purified anti-CSF antibodies. In addition to being tumoristatic, CSF-stimulated macrophages were tumoricidal as determined by a tumor colony growth assay. Tumor cells that had been incubated with CSF-stimulated macrophages showed a significant reduction in tumor colony-forming units (P less than 0.01). Thus, in addition to its effect on hemopoietic stem cells, CSF induces certain effector functions in mature macrophages that may enhance endogenous antitumor host defenses.

摘要

对集落刺激因子(CSF)刺激巨噬细胞抗肿瘤活性的能力进行了评估。用CSF孵育48小时的小鼠腹腔巨噬细胞可将P815肿瘤细胞对[3H]胸腺嘧啶核苷(TdR)的掺入抑制至对照值的约20%。CSF刺激的巨噬细胞的抑制作用明显大于未刺激的巨噬细胞(P<0.001)。CSF对肿瘤细胞或巨噬细胞单独的增殖几乎没有直接影响,这表明CSF的抗肿瘤活性是由巨噬细胞介导的。CSF制剂中的杂质不太可能是造成这种效应的原因,因为已纯化至同质的CSF与粗制制剂一样具有活性。此外,加入纯化的抗CSF抗体可阻断CSF对巨噬细胞的活性。除了具有抑瘤作用外,通过肿瘤集落生长试验确定,CSF刺激的巨噬细胞具有杀瘤作用。与CSF刺激的巨噬细胞孵育的肿瘤细胞的肿瘤集落形成单位显著减少(P<0.01)。因此,除了对造血干细胞的作用外,CSF还可诱导成熟巨噬细胞产生某些效应功能,这可能增强宿主内源性抗肿瘤防御。

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