Jcb_201408090 1..10

Tissue damage and repair involves the complex interactions between different populations of cells and their coordinated cell movement (Nathan, 2006; Silva, 2010; Sindrilaru and Scharffetter-Kochanek, 2013; Abtin et al., 2014). The mechanisms through which these interactions are orchestrated to mediate resolution of inflammation, a key step in tissue repair, remain largely unknown (Nathan and Ding, 2010). The resolution of neutrophil-mediated inflammation was classically thought to occur through controlled apoptosis (Ortega-Gómez et al., 2013). However, recent work has established that migration of neutrophils out of inflamed tissues, termed neutrophil reverse migration, is a key mechanism of local resolution (Mathias et al., 2006; Woodfin et al., 2011; Starnes and Huttenlocher, 2012; Robertson et al., 2014). Macrophages are known to regulate the resolution of neutrophil-mediated inflammation through phagocytosis of apoptotic neutrophils (Bratton and Henson, 2011). However, the role of macrophage–neutrophil interactions in reverse migration-mediated resolution is unknown. We took advantage of transparent zebrafish larvae to manipulate interactions between neutrophils and macrophages and identified a neutrophil-repelling role for macrophages during the resolution of neutrophil-mediated inflammation.