The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors

Jane Y. Wu (), Lili Feng, Hwan-Tae Park, Necat Havlioglu, Leng Wen, Hao Tang, Kevin B. Bacon, Zhi-hong Jiang, Xiao-chun Zhang and Yi Rao
Additional contact information
Jane Y. Wu: and Molecular Biology and Pharmacology
Lili Feng: Baylor College of Medicine
Hwan-Tae Park: and Molecular Biology and Pharmacology
Necat Havlioglu: and Molecular Biology and Pharmacology
Leng Wen: Washington University School of Medicine
Hao Tang: and Molecular Biology and Pharmacology
Kevin B. Bacon: Bayer Yakuhin Ltd
Zhi-hong Jiang: and Molecular Biology and Pharmacology
Xiao-chun Zhang: and Molecular Biology and Pharmacology
Yi Rao: Washington University School of Medicine

Nature, 2001, vol. 410, issue 6831, 948-952

Abstract: 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.

Date: 2001
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DOI: 10.1038/35073616

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