The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors

Migration is a basic feature of many cell types in a wide range of species( 1). Since the 1800s, cell migration has been proposed to occur in the nervo us and immune systems(2,3), and distinct molecular cues for mammalian neuro ns and leukocytes have been identified. Here we report that Slit, a secrete d protein previously known for its role of repulsion in axon guidance and n euronal migration, can also inhibit leukocyte chemotaxis induced by chemota ctic factors. Slit inhibition of the chemokine-induced chemotaxis can be re constituted by the co-expression of a chemokine receptor containing seven t ransmembrane domains and Roundabout (Robo), a Slit receptor containing a si ngle transmembrane domain. Thus, there is a functional interaction between single and seven transmembrane receptors. Our results reveal the activity o f a neuronal guidance cue in regulating leukocyte migration and indicate th at there may be a general conservation of guidance mechanisms underlying me tazoan cell migration. In addition, we have uncovered an inhibitor of leuko cyte chemotaxis, and propose a new therapeutic approach to treat diseases i nvolving leukocyte migration and chemotactic factors.