Molecular definition of distinct cytoskeletal structures involved in complement- and Fc receptor-mediated phagocytosis in macrophages.
Molecular definition of distinct cytoskeletal structures involved in complement- and Fc receptor-mediated phagocytosis in macrophages.
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巨噬细胞中涉及补体和FC受体介导的吞噬作用的不同细胞骨架结构的分子定义。
DOI：
10.1084/jem.184.2.627
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发表时间：
1996-08-01
期刊：
影响因子：
--
通讯作者：
Aderem A
中科院分区：
文献类型：
--
作者：
Allen LA;Aderem A
从超微结构研究的结果早已知道，补体和免疫球蛋白G（IgG）调理的颗粒被巨噬细胞不同地吞噬（Kaplan. G. 1977. Scand.J.Immunol.6：797-807）。补体调理的颗粒沉入细胞中，而IgG包被的颗粒被从细胞表面突出的片状伪足吞噬。这些差异的分子基础是未知的。我们使用间接免疫荧光和共聚焦显微镜检查细胞骨架蛋白如何与含有补体调理酵母聚糖（COZ）颗粒或IgG珠的phorbol-myristateacetate处理的腹腔巨噬细胞吞噬体。在COZ的摄入过程中，富含F-肌动蛋白、黏着斑蛋白、α-辅肌动蛋白、桩蛋白和含磷酸酪氨酸的蛋白质的点状结构分布在吞噬体表面。这些病灶在细胞升温至37 ℃后30 s内在结合COZ下方检测到，它们的形成需要活性蛋白激酶C。相比之下，在Fc受体介导的吞噬作用，所有的蛋白质检查均匀分布或附近的吞噬体表面。此外，摄取IgG珠被酪氨酸激酶抑制剂阻断，而COZ的吞噬作用则没有。因此，颗粒摄取所需的信号，以及吞噬体表面上的细胞骨架蛋白的排列，取决于参与的吞噬受体。此外，补体受体（CR）介导的内化需要完整的微管，并伴随着形成吞噬体下的囊泡的积累，这表明膜运输在CR介导的吞噬作用中起着关键作用。
It has long been known from the results of ultrastructural studies that complement- and immunoglobulin G (IgG)-opsonized particles are phagocytosed differently by macrophages (Kaplan. G. 1977. Scand. J. Immunol. 6:797-807). Complement-opsonized particles sink into the cell, whereas IgG-coated particles are engulfed by lamellipodia, which project from the cell surface. The molecular basis for these differences is unknown. We used indirect immunofluorescence and confocal microscopy to examine how cytoskeletal proteins associate with phagosomes containing complement-opsonized zymosan (COZ) particles or IgG beads in phorbol-myristateacetate-treated peritoneal macrophages. During ingestion of COZ, punctate structures rich in F-actin, vinculin, alpha-actinin, paxillin, and phosphotyrosine-containing proteins are distributed over the phagosome surface. These foci are detected beneath bound COZ within 30 s of warming the cells to 37 degrees C, and their formation requires active protein kinase C. By contrast, during Fc receptor-mediated phagocytosis, all proteins examined were uniformly distributed on or near the phagosome surface. Moreover, ingestion of IgG beads was blocked by tyrosine kinase inhibitors, whereas phagocytosis of COZ was not. Thus, the signals required for particle ingestion, and the arrangement of cytoskeletal proteins on the phagosome surface, vary depending upon which phagocytic receptor is engaged. Moreover, complement receptor (CR)-mediated internalization required intact microtubules and was accompanied by the accumulation of vesicles beneath the forming phagosome, suggesting that membrane trafficking plays a key role in CR-mediated phagocytosis.