Neutrophils are terminally differentiated and relatively short lived. Thus, not surprisingly, 55% to 60% of the bone marrow is dedicated to their production ( 2). Neutrophils are generated at a rate of 10 11 per day, which can increase to 10 12 per day during bacterial infection. In humans, neutrophils account for 50% to 70% of all circulating leukocytes, and they are the first line of host defense against a wide range of infectious pathogens including bacteria, fungi, and protozoa. Indeed, the survival of primitive organisms-for example, insects, which lack adaptive immune cells such as lymphocytes-relies on the function of their innate immune phagocytes ( 1).
They are the major cellular arm of the innate immune system, which is common to species throughout the evolutionary tree. Phagocytes have evolved as specialized cells that engulf and kill invading pathogens to protect the host against microorganisms. Multicellular organisms face a constant challenge of surviving in an environment containing unicellular pathogens. These newly appreciated contributions of neutrophils are described in the setting of several inflammatory and autoimmune diseases. In addition, we present more recent evidence that interactions between neutrophils and adaptive immune cells establish a feed-forward mechanism that amplifies pathologic inflammation. Here we discuss these primordial neutrophil functions, which also play key roles in tissue injury, by providing details of neutrophil cytotoxic functions and congenital disorders of neutrophils. These include the production of reactive oxygen species, the release of antimicrobial peptides, and the recently discovered expulsion of their nuclear contents to form neutrophil extracellular traps. Central to their function is their ability to be recruited to sites of infection, to recognize and phagocytose microbes, and then to kill pathogens through a combination of cytotoxic mechanisms. Neutrophils and neutrophil-like cells are the major pathogen-fighting immune cells in organisms ranging from slime molds to mammals.
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