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* Division of Cell and Molecular Biology,
Department of Physics, and
Molecular and Cellular Medicine, National Heart and Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom
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 > 
0.7 µm 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 1 µm/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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a fellowship from the Wenner-Gren Foundations (to B.Ö.), the Medical Research Council (U.K.), the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the U.K. Department of Trade and Industry (Beacon Project). D.M.D. is a recipient of a Lister Institute Research Prize.
2 Current address: Microbiology and Tumor Biology Center and Strategic Research Center for Studies of Integrated Recognition in the Immune System, Karolinska Institute, Stockholm, Sweden.
3 Address correspondence and reprint requests to Dr. Daniel M. Davis, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, London SW7 2AZ, U.K. E-mail address: d.davis{at}imperial.ac.uk
4 Abbreviations used in this paper: BCG, bacillus Calmette-Guérin; LAMP, lysosome-associated membrane protein.
5 The online version of this article contains supplemental material.
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