Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria

Structurally distinct membrane nanotubes between human macrophages support long-distance vesicular traffic or surfing of bacteria
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DOI:
10.4049/jimmunol.177.12.8476
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发表时间:
2006-12-15
影响因子:
4.4
通讯作者:
Davis, Daniel M.
Davis, Daniel M.
中科院分区:
医学2区
文献类型:
--
作者:
Onfelt, Born;Nedvetzki, Shlomo;Davis, Daniel M.

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我们报道了人单核细胞来源的巨噬细胞之间的两类膜纳米管可以通过它们的细胞骨架结构和功能特性来区分。薄膜纳米管只含有F-肌动蛋白,而较厚的纳米管,即直径类似0.7微米的纳米管,既含有F-肌动蛋白,又含有微管。细菌可以被捕获,并沿着薄但不厚的膜纳米管冲向相连的巨噬细胞体。一旦进入细胞体,细菌就可以被吞噬。细菌的移动得到了纳米管表面的结构性流动的帮助,因为链霉亲和素包裹的珠子同样能够在表面生物素化的巨噬细胞之间沿着纳米管运输。线粒体。细胞内的囊泡,包括晚期的内小体和溶酶体,可以在厚的膜纳米管中检测到,但不是薄的。动图分析表明,囊泡以类似于1微米/S的速度逐步双向移动,这与仅在厚纳米管中发现的微管介导的交通一致。在添加叠氮后,粗纳米管中的囊泡交通和珠子沿细纳米管的冲浪都被阻止,这表明这两个过程都需要ATP。然而,微管稳定剂秋水仙碱或诺康唑阻止了纳米管表面的囊泡运输,但不影响纳米管表面的流动,证实了纳米管不同的细胞骨架结构导致了不同的功能特性。因此,巨噬细胞之间的膜纳米管比一成不变的无处不在的膜纽带更复杂,并有助于免疫细胞之间远端相互作用的几种方式。
We report that two classes of membrane nanotubes between human monocyte-derived macrophages can be distinguished by their cytoskeletal structure and their functional properties. Thin membrane nanotubes contained only F-actin, whereas thicker nanotubes, i.e., those > similar to 0.7 mu m in diameter, contained both F-actin and microtubules. Bacteria could be trapped and surf along thin, but not thick, membrane nanotubes toward connected macrophage cell bodies. Once at the cell body, bacteria could then be phagocytosed. The movement of bacteria is aided by a constitutive flow of the nanotube surface because streptavidin-coated beads were similarly able to traffic along nanotubes between surface-biotinylated macrophages. Mitochondria. and intracellular vesicles, including late endosomes and lysosomes, could be detected within thick, but not thin, membrane nanotubes. Analysis from kymographs demonstrated that vesicles moved in a stepwise, bidirectional manner at similar to 1 mu m/s, consistent with their traffic being mediated by the microtubules found only in thick nanotubes. Vesicular traffic in thick nanotubes and surfing of beads along thin nanotubes were both stopped upon the addition of azide, demonstrating that both processes require ATP. However, microtubule destabilizing agents colchicine or nocodazole abrogated vesicular transport but not the flow of the nanotube surface, confirming that distinct cytoskeletal structures of nanotubes give rise to different functional properties. Thus, membrane nanotubes between macrophages are more complex than unvarying ubiquitous membrane tethers and facilitate several means for distal interactions between immune cells.