Visualizing the function and fate of neutrophils in sterile injury and repair

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Imaging the unforeseen fate of neutrophilsInflammation that results from insults such as ischemia and reperfusion or trauma in the absence of microorganisms is known as “sterile inflammation.” Neutrophils are recruited in vast numbers during sterile inflammation and have been thought to play a detrimental role. Wang et al. used intravital microscopy to show that neutrophils actually perform helpful tasks such as removing and regenerating thermally damaged blood vessels in the liver (see the Perspective by Garner and de Visser). Moreover, neutrophils neither die nor are phagocytosed. Instead, they return to the circulation in a process called “reverse transmigration,” making a pit stop in the lungs, before ending their lives where they began—in the bone marrow. Thus, a reconsideration of the use of anti-neutrophil therapies after injury may be warranted.Science, this issue p. 111; see also p. 42Neutrophils have been implicated as harmful cells in a variety of inappropriate inflammatory conditions where they injure the host, leading to the death of the neutrophils and their subsequent phagocytosis by monocytes and macrophages. Here we show that in a fully repairing sterile thermal hepatic injury, neutrophils also penetrate the injury site and perform the critical tasks of dismantling injured vessels and creating channels for new vascular regrowth. Upon completion of these tasks, they neither die at the injury site nor are phagocytosed. Instead, many of these neutrophils reenter the vasculature and have a preprogrammed journey that entails a sojourn in the lungs to up-regulate CXCR4 (C-X-C motif chemokine receptor 4) before entering the bone marrow, where they undergo apoptosis.

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