DIFFERENTIAL INDUCTION OF ACTIVATION MARKERS IN MACROPHAGE CELL-LINES BY INTERFERON-GAMMA
DIFFERENTIAL INDUCTION OF ACTIVATION MARKERS IN MACROPHAGE CELL-LINES BY INTERFERON-GAMMA
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DOI：
10.1016/0008-8749(89)90208-6
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发表时间：
1989-05-01
影响因子：
4.3
通讯作者：
PAULNOCK, DM
中科院分区：
文献类型：
--
作者：
LAMBERT, LE;PAULNOCK, DM
在这些研究中使用巨噬细胞系作为模型来剖析巨噬细胞活化过程的生物化学和功能性线粒体。特别地，干扰素-γ在RAW 264.7和WEHI-3细胞系中诱导杀肿瘤和杀菌活性的要求是：（IFN-γ）和细菌脂多糖（LPS）的测定。在细胞刺激期间监测传统上与巨噬细胞活化相关的一系列巨噬细胞标志物表达的变化，以确定活化相关变化的可检测模式是否与特定功能活性的发展相关。这些标志物包括主要组织相容性复合体编码的I类和II类抗原以及mac-1/LFA-1家族中抗原的细胞表面表达的变化、膜酶（5”核苷酸酶和碱性磷酸二酯酶）水平的改变以及分泌产物的产生，包括过氧化氢和单核因子白细胞介素-1、干扰素-α/。例如β，和肿瘤坏死因子-α。我们的结果表明，给定的同质巨噬细胞群体响应于单一的、确定的激活信号如IFN-γ表达功能活性的不同子集。还有LPS。多种巨噬细胞表面抗原、酶和分泌产物的展示通过这样的处理被同时激活;然而，这样的激活相关标志物的特定模式不能可重复地用于预测激活的细胞执行特定功能的能力。结果还表明，表达IFN-γ后的不同应答模式的巨噬细胞系。刺激为巨噬细胞活化的分子和细胞生物学的解剖提供了有价值的系统。
Macrophage cell lines were used in these studies as a model to dissect the biochemical and functional miosaic of the macrophage activation process. In particular, the requirements for the induction of tumoricidal and bactericidal activity in the RAW 264.7 and WEHI-3 cell lines by interferon-.gamma. (IFN-.gamma.) and bacterial lipopolysaccharide (LPS) were determined. Changes in expression of a series of macrophage markers traditionally associated with macrophage activation were monitored during stimulation of the cells in order to determine whether a detectable pattern of activation-associated changes is associated with the development of a particular functional activity. These markers included changes in the cell surface expression of major histocompatibility complex-encoded Class I and Class II antigens and antigens in the mac-1/LFA-1 family, alterations in the levels of membrane enzymes (5'' nucleotidase and alkaline phosphodiesterase), and production of secretory products including hydrogen peroxide and the monokines interleukin-1, interferons-.alpha./.beta., and tumor necrosis factor-.alpha.. Our results demonstrate that a given homogeneous macrophage population expresses a distinct subset of functional activities in response to single, defined activating signals such as IFN-.gamma. and LPS. The display of a variety of macrophage surface antigens, enzymes, and secreted products is activated simultaneously by such treatment; however, the particular pattern of such activation-associated markers cannot reproducibly be used to predict the ability of an activated cell to perform a particular function. The results also suggest that macrophage cell lines expressing differential response patterns following IFN-.gamma. stimulation provide a valuable system for dissection of the molecular and cell biology of macrophage activation.