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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >IDENTIFICATION OF AN INDUCIBLE SURFACE MOLECULE SPECIFIC TO FUSING MACROPHAGES
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IDENTIFICATION OF AN INDUCIBLE SURFACE MOLECULE SPECIFIC TO FUSING MACROPHAGES

机译:识别特定于融合巨噬细胞的表面分子

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Multinucleated giant cells and osteoclasts arise through the fusion of mononuclear phagocyte precursors, To elucidate the mechanism by which cells of monocytic lineage fuse and differentiate into giant cells and osteoclasts, we hypothesized that, as with other cell fusion events, specific surface molecules mediate the adhesion/fusion process, it has been observed that macrophages can be induced to fuse with one another in response to specific stimuli or when placed in a specific microenvironment. The formation of giant cells is primarily associated with chronic inflammatory reactions and tumors, while osteoclasts differentiate on bone which they resorb, The fact that, under normal conditions, macrophages and monocytes fail to fuse in regions and tissues where they are present in large numbers suggests the regulated and transient expression of potential fusion molecules, To identify such a fusion-associated molecule, we established a macrophage fusion assay and generated monoclonal antibodies (mAbs) that alter the fusion of macrophages in vitro. We selected four mAbs that each had the ability to block the fusion but not the aggregation of macrophages ill vitro. All four antibodies recognize surface proteins of 150 kDa, The expression of the antigens recognized by all four mAbs is restricted to macrophages that have been induced to fuse in vitro and in vivo and is inducible, transient, and regulated, as neither nonfusing macrophages nor macrophages fused in vitro express these antigens, These results support the hypothesis that macrophage fusion is mediated by specific fusion/adhesion molecules and also provide a means to study the molecular mechanisms of macrophage fusion.
机译:多核巨细胞和破骨细胞通过单核吞噬细胞前体的融合而产生。为了阐明单核细胞系细胞融合并分化为巨细胞和破骨细胞的机制,我们假设与其他细胞融合事件一样,特定的表面分子介导了粘附在融合过程中,已经观察到巨噬细胞可以响应于特定的刺激或置于特定的微环境中而相互融合。巨细胞的形成主要与慢性炎症反应和肿瘤有关,而破骨细胞则在它们吸收的骨骼上分化。在正常情况下,巨噬细胞和单核细胞无法在大量存在的区域和组织中融合的事实表明潜在融合分子的调控和瞬时表达,为了鉴定这种融合相关分子,我们建立了巨噬细胞融合测定法,并产生了可在体外改变巨噬细胞融合的单克隆抗体(mAb)。我们选择了四个mAb,每个mAb在体外都具有阻止融合但不阻止巨噬细胞聚集的能力。所有四种抗体均识别150 kDa的表面蛋白。所有四种mAb识别的抗原的表达仅限于巨噬细胞,这些巨噬细胞已被诱导在体内和体外融合,并且可以作为非融合巨噬细胞或巨噬细胞进行诱导,瞬时和调节体外融合表达这些抗原。这些结果支持以下假设,即巨噬细胞融合是由特定的融合/粘附分子介导的,并提供了研究巨噬细胞融合的分子机制的手段。

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