The Healing Power of Neutrophils

Tissue-restorative and proangiogenic functions of neutrophils have been uncovered in models of sterile and ischemic injury, as well as in tumors. Neutrophils are important for limiting microbial invasion at sites of skin or mucosal injury, but they also contribute to tissue restoration during wound healing. At the site of injury, neutrophils initiate healing via direct effects on angiogenesis and cell proliferation. The healing capacities of neutrophils are impaired in patients with chronic diseases associated with compromised healing, such as in diabetes. Understanding the contributions of neutrophils to the healing of different types of injuries will help to uncover potential targets that might be therapeutically exploited in disease states where tissue healing can be compromised. Neutrophils promptly accumulate in large numbers at sites of tissue injury. Injuries to the skin or mucosae disrupt barriers against the external environment, and the bactericidal actions of neutrophils are important in preventing microbial invasion. Neutrophils have also been associated with exacerbated inflammation, for example in non-healing wounds or in conditions such as inflammatory bowel disease (IBD). However, additional neutrophil functions important for angiogenesis and tissue restoration have been uncovered in models of sterile and ischemic injury, as well as in tumors. These functions are also relevant in healing skin and mucosal wounds, and can be impaired in conditions associated with non-healing wounds, such as diabetes. Here, we discuss our current understanding of neutrophil contributions to healing, and how the latter can be compromised in disease. Neutrophils promptly accumulate in large numbers at sites of tissue injury. Injuries to the skin or mucosae disrupt barriers against the external environment, and the bactericidal actions of neutrophils are important in preventing microbial invasion. Neutrophils have also been associated with exacerbated inflammation, for example in non-healing wounds or in conditions such as inflammatory bowel disease (IBD). However, additional neutrophil functions important for angiogenesis and tissue restoration have been uncovered in models of sterile and ischemic injury, as well as in tumors. These functions are also relevant in healing skin and mucosal wounds, and can be impaired in conditions associated with non-healing wounds, such as diabetes. Here, we discuss our current understanding of neutrophil contributions to healing, and how the latter can be compromised in disease. protein complexes that bind neighboring epithelial or endothelial cells together and whose cytoplasmic portion is linked to the actin cytoskeleton. polysaccharide-producing bacteria attaching to each other and to a surface. neutrophils can release granules that contain antibacterial agents including MPO, defensins, lysozyme, serine proteases, and lactoferrin. specifically displayed on the surface of apoptotic cells for their selective clearance by macrophages through phagocytosis. the process by which dying cells are cleared by macrophages. a condition in which elevated concentrations of lipids are found in the blood circulation as a result of diet and lifestyle. formed on the surface of wounds during the healing process; granulation tissue comprises connective tissue and blood vessels. a group of transcription factors that respond to locally reduced oxygen concentrations and which mediate the effects of hypoxia. invaginations of the intestinal mucosa covered by different epithelial cells, for example intestinal stem cells that are found at the base of the crypt. tissue damage observed when blood supply returns following a period of ischemia (oxygen deprivation). a cytotoxic enzyme that is abundantly expressed by neutrophils and, upon degranulation, is released into the extracellular space to kill pathogens. vascular smooth muscle cells and pericytes located around blood vessels; mural cells are important for vascular development and stability. first responders to sites of inflammation harboring antitumor activity through the production and release of proinflammatory chemokines and cytokines. neutrophils recruited at later timepoints following injury compared to N1; they are believed to contribute to healing via active phagocytosis. neutrophils can release their DNA into the extracellular space where it forms a network decorated with antibacterial neutrophil-derived proteins to kill bacteria. a key mediator complex of the innate immune system; the inflammasome is activated by danger signals from damaged cells or pathogens. a mural cell that wraps around the microvasculature and is embedded in the basement membrane; it communicates with endothelial cells to stabilize blood vessels. migration of immune cells from tissues into the blood circulation. secretory proteins within the mucus lining of the gastrointestinal mucosa that are believed to contribute to healing the mucosal epithelium. a consequence of myocardial infarction that is believed to reduce ventricular wall strength owing to high concentrations of matrix metalloproteinases.