Evans R, Kamdar S J, Fuller J A, Krupke D M
Jackson Laboratory, Bar Harbor, Maine 04609, USA.
J Leukoc Biol. 1995 Jul;58(1):99-107. doi: 10.1002/jlb.58.1.99.
In this report we report that recombinant human monocyte-macrophage colony-stimulating factor-1 (CSF-1) induces resident murine peritoneal cells (PCs) to transcribe several inflammatory cytokine genes, including interleukin (IL)-1 alpha, IL-1 beta, IL-6, and granulocyte-macrophage CSF in a dose-dependent and time-related manner. Peak mRNA levels were seen between 4 and 6 h. CSF-1 did not modulate the expression of tumor necrosis factor-alpha mRNA. The serum content of the culture medium appeared to regulate both the extent of CSF-1-induced gene transcription and the adherence properties of the cells. Decreasing the serum concentration significantly reduced CSF-1-induced transcription and was associated with the rapid spreading of the majority of the adherent cells. This reduced sensitivity to CSF-1 was paralleled by a markedly lower levels of c-fms mRNA encoding the CSF-1 receptor. Induced gene transcription was followed by the release of large quantities of IL-6 only. IL-1 activity remained associated with the cells. Neither supernatant nor cell lysate granulocyte-macrophage CSF activity was inducible above the low levels associated with control cultures. Evidence that the mononuclear phagocytes, as opposed to B or T cells, were the targets of CSF-1 was obtained in two ways: (1) PCs from B6 scid/scid and NOD scid/scid mice consisting of 78-86% MAC-1+, F4/80+ cells and few B or T cells, as shown by flow cytometry analysis, released 5- to 10-fold more IL-6 in response to CSF-1 stimulation than B6 PCs, which contained approximately 30% double-positive cells, and (2) pretreatment of B6 PCs with antibodies to the CSF-1 receptor blocked the CSF-1-induced secretion of IL-6. These data suggest that CSF-1 primes noninflammatory mononuclear phagocytes for a role in inflammatory responses but does not provide the necessary signals for either secretion or translation of all cytokines equally.
在本报告中，我们报道重组人单核细胞 - 巨噬细胞集落刺激因子 -1（CSF-1）以剂量依赖性和时间相关性方式诱导驻留的小鼠腹膜细胞（PCs）转录多种炎性细胞因子基因，包括白细胞介素（IL）-1α、IL-1β、IL-6和粒细胞 - 巨噬细胞集落刺激因子。在4至6小时之间观察到mRNA水平峰值。CSF-1未调节肿瘤坏死因子 -αmRNA的表达。培养基的血清含量似乎调节CSF-1诱导的基因转录程度以及细胞的黏附特性。降低血清浓度显著降低CSF-1诱导的转录，并与大多数贴壁细胞的快速铺展相关。这种对CSF-1敏感性的降低与编码CSF-1受体的c-fms mRNA水平明显降低平行。诱导的基因转录之后仅释放大量的IL-6。IL-1活性仍与细胞相关。上清液和细胞裂解物中的粒细胞 - 巨噬细胞集落刺激因子活性均不能诱导至高于与对照培养物相关的低水平。通过两种方式获得证据表明单核吞噬细胞而非B或T细胞是CSF-1的靶标：（1）流式细胞术分析显示，来自B6 scid/scid和NOD scid/scid小鼠的PCs由78 - 86%的MAC-1+、F4/80+细胞和少量B或T细胞组成，与含有约30%双阳性细胞的B6 PCs相比，对CSF-1刺激的反应释放的IL-6多5至10倍；（2）用抗CSF-1受体抗体预处理B6 PCs可阻断CSF-1诱导的IL-6分泌。这些数据表明，CSF-1使非炎性单核吞噬细胞在炎症反应中发挥作用，但并非为所有细胞因子的分泌或翻译均提供必要信号。
