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The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors

Nature volume 410, pages 948–952 (2001)Cite this article

Abstract

Migration is a basic feature of many cell types in a wide range of species1. Since the 1800s, cell migration has been proposed to occur in the nervous and immune systems2,3, and distinct molecular cues for mammalian neurons and leukocytes have been identified. Here we report that Slit, a secreted protein previously known for its role of repulsion in axon guidance and neuronal migration, can also inhibit leukocyte chemotaxis induced by chemotactic factors. Slit inhibition of the chemokine-induced chemotaxis can be reconstituted by the co-expression of a chemokine receptor containing seven transmembrane domains and Roundabout (Robo), a Slit receptor containing a single transmembrane domain. Thus, there is a functional interaction between single and seven transmembrane receptors. Our results reveal the activity of a neuronal guidance cue in regulating leukocyte migration and indicate that there may be a general conservation of guidance mechanisms underlying metazoan cell migration. In addition, we have uncovered an inhibitor of leukocyte chemotaxis, and propose a new therapeutic approach to treat diseases involving leukocyte migration and chemotactic factors.

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Figure 1: Expression of Slit and Robo in adult tissues.
Figure 2: Effect of Slit on leukocyte chemotaxis induced by SDF-1α.
Figure 3: Robo is involved in mediating Slit inhibition of chemotaxis.
Figure 4: Lack of general inhibition by Slit.

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Acknowledgements

The amount of data presented and the number papers cited have been limited by space constraints. We are grateful to X. He for help with FACS; to W. Smith for providing us with the HL60 cell line; to the NIH for grant support (to J.Y.W., L.F. and Y.R.); to the John Merck fund, the Klingenstein foundation, and the Leukemia Society of America for scholar awards (to Y.R. and J.Y.W.).

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Authors and Affiliations

  1. Departments of Pediatrics, and Molecular Biology and Pharmacology,

    Jane Y. Wu, Hwan-Tae Park, Necat Havlioglu, Hao Tang, Zhi-hong Jiang & Xiao-chun Zhang

  2. Department of Anatomy and Neurobiology, Washington University School of Medicine, Box 8108, 660 S. Euclid Avenue, St Louis, 63110, Missouri, USA

    Leng Wen & Yi Rao

  3. Department of Medicine, Division of Nephrology, Baylor College of Medicine, One Baylor Plaza, Houston, N730 77030, Texas, USA

    Lili Feng

  4. Department of Biology I, Bayer Yakuhin Ltd, 6-5-1-3 Kunimidai, Kizu-cho, Soraku-gun, Kyoto, Japan

    Kevin B. Bacon

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  1. Jane Y. Wu
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Correspondence to Jane Y. Wu.

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Wu, J., Feng, L., Park, HT. et al. The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature 410, 948–952 (2001). https://doi.org/10.1038/35073616

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