Neutrophils cascading their way to inflammation
TL;DR: Current data suggest that neutrophil chemoattractants have unique functions in the recruitment of neutrophils into inflammatory sites in vivo, dictated by their distinct patterns of temporal and spatial expression.
About: This article is published in Trends in Immunology.The article was published on 2011-10-01 and is currently open access. It has received 486 citations till now. The article focuses on the topics: Innate immune system.
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TL;DR: The key features of the life of a neutrophil are discussed, from its release from bone marrow to its death, and the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites are explained.
Abstract: Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
3,898 citations
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...When activated by chemoattractants, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) into phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the leading edge of neutrophils 102, and this promotes their directional migration....
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TL;DR: Primordial neutrophil functions are discussed, and more recent evidence that interactions between neutrophils and adaptive immune cells establish a feed-forward mechanism that amplifies pathologic inflammation is presented.
Abstract: Neutrophils and neutrophil-like cells are the major pathogen-fighting immune cells in organisms ranging from slime molds to mammals. 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. 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. 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. In addition, we present more recent evidence that interactions between neutrophils and adaptive immune cells establish a feed-forward mechanism that amplifies pathologic inflammation. These newly appreciated contributions of neutrophils are described in the setting of several inflammatory and autoimmune diseases.
914 citations
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...Amazingly, neutrophils can detect and respond to complex gradients of chemoattractants, which provide graded intracellular signaling responses, allowing the cells to reach the site of pathogen invasion (91, 92)....
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TL;DR: The different cues within tissues that mediate neutrophil forward and reverse migration in response to injury or infection are discussed and the implications of these mechanisms to human disease are discussed.
Abstract: Neutrophil migration and its role during inflammation has been the focus of increased interest in the past decade. Advances in live imaging and the use of new model systems have helped to uncover the behaviour of neutrophils in injured and infected tissues. Although neutrophils were considered to be short-lived effector cells that undergo apoptosis in damaged tissues, recent evidence suggests that neutrophil behaviour is more complex and, in some settings, neutrophils might leave sites of tissue injury and migrate back into the vasculature. The role of reverse migration and its contribution to resolution of inflammation remains unclear. In this Review, we discuss the different cues within tissues that mediate neutrophil forward and reverse migration in response to injury or infection and the implications of these mechanisms to human disease.
673 citations
TL;DR: The definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease are reviewed and diagrams of the mechanisms of disease are provided.
612 citations
Cites background from "Neutrophils cascading their way to ..."
...potent chemokines for these leukocytes.(213-217) The primary cells and tissues responsible for an intraamniotic inflammatory response include fetal skin, cells that comprise the chorioamniotic membranes, and the umbilical cord....
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TL;DR: The beneficial and deleterious roles of neutrophils in the intestine during health and disease are summarized and an overview of what is known about neutrophil function in the gut is provided.
522 citations
References
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TL;DR: This Review focuses on new aspects of one of the central paradigms of inflammation and immunity — the leukocyte adhesion cascade.
Abstract: To get to the site of inflammation, leukocytes must first adhere to and traverse the blood-vessel wall, events that occur in a cascade-like manner. But what are the exact steps in this cascade and what molecules are involved?
3,917 citations
TL;DR: Progression of COPD is associated with the accumulation of inflammatory mucous exudates in the lumen and infiltration of the wall by innate and adaptive inflammatory immune cells that form lymphoid follicles, coupled to a repair or remodeling process that thickens the walls of these airways.
Abstract: Background Chronic obstructive pulmonary disease (COPD) is a major public health problem associated with long-term exposure to toxic gases and particles. We examined the evolution of the pathological effects of airway obstruction in patients with COPD. Methods The small airways were assessed in surgically resected lung tissue from 159 patients — 39 with stage 0 (at risk), 39 with stage 1, 22 with stage 2, 16 with stage 3, and 43 with stage 4 (very severe) COPD, according to the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Results The progression of COPD was strongly associated with an increase in the volume of tissue in the wall (P<0.001) and the accumulation of inflammatory mucous exudates in the lumen (P<0.001) of the small airways. The percentage of the airways that contained polymorphonuclear neutrophils (P<0.001), macrophages (P<0.001), CD4 cells (P=0.02), CD8 cells (P=0.038), B cells (P<0.001), and lymphoid aggregates containing follicles (P=0.003) and the abs...
3,401 citations
TL;DR: Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myeloperoxidase, but this is incorrect.
Abstract: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi. Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myeloperoxidase. We now know this is incorrect. The oxidase pumps electrons into the phagocytic vacuole, thereby inducing a charge across the membrane that must be compensated. The movement of compensating ions produces conditions in the vacuole conducive to microbial killing and digestion by enzymes released into the vacuole from the cytoplasmic granules.
1,672 citations
TL;DR: In blood, Ccr2−/− monocytes could traffic to sites of infection, demonstrating that CCR2 is not required for migration from the circulation into tissues, and determining the frequency of Ly6Chi monocytes in the circulation.
Abstract: Monocytes recruited to tissues mediate defense against microbes or contribute to inflammatory diseases Regulation of the number of circulating monocytes thus has implications for disease pathogenesis However, the mechanisms controlling monocyte emigration from the bone marrow niche where they are generated remain undefined We demonstrate here that the chemokine receptor CCR2 was required for emigration of Ly6C(hi) monocytes from bone marrow Ccr2(-/-) mice had fewer circulating Ly6C(hi) monocytes and, after infection with Listeria monocytogenes, accumulated activated monocytes in bone marrow In blood, Ccr2(-/-) monocytes could traffic to sites of infection, demonstrating that CCR2 is not required for migration from the circulation into tissues Thus, CCR2-mediated signals in bone marrow determine the frequency of Ly6C(hi) monocytes in the circulation
1,489 citations
TL;DR: Neutrophils are produced in the bone marrow from stem cells that proliferate and differentiate to mature neutrophils fully equipped with an armory of granules that contain proteins that enable the neutrophil to deliver lethal hits against microorganisms, but also to cause great tissue damage.
1,251 citations