The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors
- 1 April 2001
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 410 (6831), 948-952
- https://doi.org/10.1038/35073616
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.Keywords
This publication has 30 references indexed in Scilit:
- The history of radial gliaBrain Research Bulletin, 1999
- Chemokines — Chemotactic Cytokines That Mediate InflammationNew England Journal of Medicine, 1998
- A Broad-Spectrum Chemokine Antagonist Encoded by Kaposi's Sarcoma-Associated HerpesvirusScience, 1997
- Poxvirus Genomes Encode a Secreted, Soluble Protein That Preferentially Inhibits β Chemokine Activity yet Lacks Sequence Homology to Known Chemokine ReceptorsVirology, 1997
- Chemotactic Peptide N-formyl-Met-Leu-Phe Activation of p38 Mitogen-activated Protein Kinase (MAPK) and MAPK-activated Protein Kinase-2 in Human NeutrophilsPublished by Elsevier BV ,1997
- The Molecular Biology of Leukocyte Chemoattractant ReceptorsAnnual Review of Immunology, 1994
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994
- Principles of neural cell migrationCellular and Molecular Life Sciences, 1990
- slit: An EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous systemCell, 1988
- Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide.The Journal of Experimental Medicine, 1979