Tauzin et al. describe how macrophages resolve inflammation by inducing neutrophils to leave wounded tissue.
Zebrafish neutrophils are attracted to wounds by reactive oxygen species (ROS) that activate the Src family kinase Lyn. Neutrophil-mediated inflammation is partly resolved by apoptosis and the cells’ subsequent engulfment by macrophages. But neutrophils can also elect to leave wounded tissue in a process known as reverse migration. Whether macrophages promote this mode of inflammation resolution is unknown.
Tauzin et al. found that neutrophils were generally recruited to wounds before macrophages, but, once they arrived, macrophages often contacted neutrophils and appeared to shepherd them away from the damaged tissue. Neutrophils remained in wounds for longer times in zebrafish larvae lacking macrophages, the researchers discovered.
Like neutrophils, macrophages were attracted to wounds by ROS and Src family kinase signaling. Macrophages lacking the p22phox subunit of NADPH oxidase complex 2 (Nox2) or the tyrosine kinase Yrk were unable to migrate into wounds and induce the departure of neutrophils.
Mutations in the human homologue of NOX2 cause chronic granulomatous disease, one symptom of which is enhanced neutrophil-mediated inflammation. Tauzin et al.’s findings suggest that this may be due to defects in macrophage recruitment and the induction of neutrophil reverse migration. Senior author Anna Huttenlocher now wants to investigate how macrophages drive neutrophils out of wounded tissue. She thinks the process may involve a combination of contact repulsion and chemokine signaling.
Text by Ben Short