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Neutrophil Reverse Migration Becomes Transparent with Zebrafish

DOI: 10.1155/2012/398640

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The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo. 1. Introduction “Certain of the lower animals, transparent enough to be observed alive, clearly show in their midst a host of small cells with moving extensions. In these animals the smallest lesion brings an accumulation of these elements at the point of damage. In small transparent larvae, it can easily be shown that the moving cells, reunited at the damage point do often close over foreign bodies [1].” Ilya Mechnikov, one of the fathers of immunology, spoke these words at his Nobel Prize lecture in 1908. More than one hundred years after his seminal studies using transparent starfish larvae to illuminate a role for phagocytosis in immunity, we are again exploiting the power of transparent larvae for research on the immune system. Studies of neutrophils in both humans and mammalian model systems have brought great advances in our knowledge of their functions; however, zebrafish, a small tropical fish with transparent larvae, have demonstrated that direct observation of neutrophils in live animals can provide important insights that would have otherwise faced significant technical challenges using mice. Neutrophils are the most abundant leukocytes in both humans and zebrafish, and they are critical for defending the host against microbial infection [2]. In response to wounding, infection, or other inflammatory stimuli, neutrophils are rapidly recruited to perform their well-known effector functions: degranulation, phagocytosis, production of reactive oxygen species (ROS), secretion of proinflammatory cytokines, and extrusion of neutrophil extracellular traps (NETs) [3, 4]. These responses are acknowledged to kill and sequester microorganisms at their site of entry and promote the activation of the adaptive immune


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