| The recruitment of neutrophils to sites of inflammation is critical for host defense. However, neutrophil-mediated tissue damage is also a significant source of injury in many inflammatory conditions, including ischemia-reperfusion injury and rheumatoid arthritis. A localized, general inhibition of chemokines, the molecules that guide leukocyte trafficking, could be a useful strategy to combat inflammatory damage. Slit-2, together with its receptor, Roundabout, inhibit neuronal migration during development. Recent evidence suggests that Slit/Robo may also inhibit the migration of some leukocyte subsets. Here, we demonstrate that Slit-2 inhibits neutrophil chemotaxis by suppressing the activation of Rho GTPases Cdc42 and Rac2. However, Slit-2 does not significantly affect other neutrophil functions. Fcgamma-mediated phagocytosis, and adhesion to fibronectin surfaces and endothelial cells are not affected by Slit-2 treament, while superoxide production is mildly upregulated. Therefore, targeted delivery of Slit-2 could potentially inhibit localized inflammatory damage without generally suppressing systemic neutrophil function. |
