Macrophage fusion induced by IL-4 alternative activation is a multistage process involving multiple target molecules
Macrophage fusion induced by IL-4 alternative activation is a multistage process involving multiple target molecules
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DOI：
10.1002/eji.200636788
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Gordon, Siamon
中科院分区：
文献类型：
--
作者：
Helming, Laura;Gordon, Siamon
多核巨细胞是肉芽肿感染的特征，起源于巨噬细胞的融合，然而，对其潜在的机制知之甚少。暴露于IL-4和IL-13的巨噬细胞的选择性活化诱导巨噬细胞同核体的形成。我们建立了一种新的定量双荧光系统来研究il -4诱导小鼠原代巨噬细胞的体外融合。通过这个实验，我们可以证明巨噬细胞融合不是由单个分子介导的，而是涉及多个功能成分。虽然一些小鼠巨噬细胞群体不能形成巨细胞，表明它们不能表现出完整的融合机制，但这些非融合性巨噬细胞可以以异源性的方式与融合能力巨噬细胞融合。由于两个融合体都需要IL-4诱导分子，因此我们得出结论，至少有两种功能不同的分子介导巨噬细胞同核体的形成，每种分子都存在于一个融合体上。此外，尽管IL-4处理导致巨噬细胞诱导融合状态，但巨噬细胞只有在粘附于允许基质时才能有效融合。基于我们的研究结果，我们得出结论，巨噬细胞融合是一个涉及多个目标分子的多阶段过程。我们描述的模型将允许分析膜融合的分子基础，并可能深入了解巨噬细胞的替代激活。
Multinucleated giant cells, characteristic of granulomatous infections, originate from fusion of macrophages, however, little is known about the underlying mechanism. Alternative activation of macrophages by exposure to IL-4 and IL-13 induces macrophage homokaryon formation. We have established a new quantitative bifluorescent system to study IL-4-induced fusion of primary murine macrophages in vitro. Using this assay, we could show that macrophage fusion is not mediated by a single molecule, but involves multiple functional components. Although several murine macrophage populations were not competent to form giant cells, indicating that they fail to display the full fusion machinery, these non-fusogenic macrophages could fuse with fusion-competent macrophages in a heterophilic manner. Since IL-4 induced molecules were needed on both fusion partners, we conclude that at least two functionally distinct molecules mediate macrophage homokaryon formation with each present on one fusion partner. In addition, though IL-4 treatment led to induction of a fusogenic status, macrophages could only fuse efficiently when adherent to a permissive substratum. Based on our findings, we conclude that macrophage fusion is a multistage process involving multiple target molecules. The model we describe will allow analysis of the molecular basis of membrane fusion and possible insight into alternative activation of macrophages.