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Papers by Karine Jéssica Santana

GED gastroenterol. …, 2006

Base de dados : LILACS. Pesquisa : 530081 [Identificador único]. Referências encontradas : 1 [ref... more Base de dados : LILACS. Pesquisa : 530081 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 530081. ...

The neutrophil patrols the blood in continuous search of prey, which presents itself primarily in... more The neutrophil patrols the blood in continuous search of prey, which presents itself primarily in the form of bacteria or dead and dying host cells. Because more than 4 trillion bacteria have colonized each human, particularly at the mucosal and skin surfaces, the task of preventing pathogen invasion is not trivial. In more than half a million people in North America each year, this system fails and severe sepsis ensues, killing approximately one-third of these people. Therefore, understanding the behavior of the immune system in response to pathogens, particularly the role of neutrophils, is essential. There is much urgency in this regard, as antibiotic-resistant bacteria such as Staphylococcus aureus and multidrug-resistant Gram-negative bacilli are on the rise, and viruses (such as the SARS corona virus and H5N1 and H1N1 influenza viruses) that make the host more susceptible to secondary infections are also becoming more prominent. Tweaking host immunity may be a way to fight these emerging pathogens. In addition to the inflammation that occurs in blood vessels as a result of infection, inflammation can also occur intravascularly as a consequence of cell death or sterile injury. Whether the neutrophil can discriminate between a sterile injury and an infection is not clear, but the molecular mechanisms mediating neutrophil recruitment can be quite variable. Ultimately, to perform their functions, neutrophils need to know where to go. Therefore, efficient neutrophil guidance through the vasculature and into the affected tissue site is crucial and is normally governed by chemotactic gradients. During sys-temic infection, this system is altered, as the highest concentrations of chemokines and other chemotactic agents are found in plasma. This reverse chemotactic gradient results in activated neutrophils within the vasculature. For many years, the prevailing view was that these neutrophils get stuck in the capillary beds of lungs and liver where they release their cytotoxic contents, which induce inappropriate tissue injury leading to multiorgan failure. However, recently, other explanations have been put forth that suggest that sequestra-tion of neutrophils in lungs and liver is beneficial to host survival. New and somewhat unorthodox ways by which neutrophils may fight bacterial infections in the blood have been described. As one example, neutrophils have been shown to expel their DNA to form neutrophil extracellular traps (NETs) to ensnare bacteria before dying. Interactions between platelets and neutrophils are essential for this process to occur in the vasculature. This review discusses recent work pertaining to neutrophil recruitment and functions during both sterile injury and infectious stimuli. We use sepsis as an example of the war between neutrophils and bacteria and the intriguing approaches that are implemented as the host and pathogen each attempt to get the upper hand. We also discuss the emerging roles of neutrophils during tissue repair and angiogen-esis. Many of these discoveries rely on experimental mouse models of inflammation and newly evolving imaging technology, and we pay particular attention to these studies. However, it is noteworthy that the relevance of many of these observations in mice remains to be confirmed in humans. Neutrophil recruitment to sites of local infection Over the last few years, the multistep process of neutrophil recruitment from blood to tissue has been extensively studied using various in vivo microscopy approaches (summarized in Fig. 1). In vivo spinning-disk confocal, laser-scanning confocal and two-photon microscopy have enabled the refined, high-resolution examination of neutrophil behavior in the context of other cells and allowed researchers to follow the interactions of neutrophils with the surrounding endothelium and interendothelial junctions, as well as their behavior as they emigrate from the vasculature. Here we focus on how neutrophils have a key regulatory role in vascular inflammation. Recent studies using advanced imaging techniques have yielded new insights into the mechanisms by which neutrophils contribute to defense against bacterial infections and also against sterile injury. In these settings, neutrophils are recruited by various mechanisms depending on the situation. We also describe how these processes may be disrupted in systemic infections, with a particular emphasis on mouse models of sepsis. Neutrophils are often immobilized in the lungs and liver during systemic infections, and this immobilization may be a mechanism through which bacteria can evade the innate immune response or allow neutrophils to form neutrophil extracellular traps that trap and kill bacteria in blood. The platelet is also an important player in sepsis, and we describe how it collaborates with neutrophils in the formation of neutrophil extracellular traps.

GED gastroenterol. …, 2006

Base de dados : LILACS. Pesquisa : 530081 [Identificador único]. Referências encontradas : 1 [ref... more Base de dados : LILACS. Pesquisa : 530081 [Identificador único]. Referências encontradas : 1 [refinar]. Mostrando: 1 .. 1 no formato [Detalhado]. página 1 de 1, 1 / 1, LILACS, seleciona. para imprimir. Fotocópia. experimental, Documentos relacionados. Id: 530081. ...

The neutrophil patrols the blood in continuous search of prey, which presents itself primarily in... more The neutrophil patrols the blood in continuous search of prey, which presents itself primarily in the form of bacteria or dead and dying host cells. Because more than 4 trillion bacteria have colonized each human, particularly at the mucosal and skin surfaces, the task of preventing pathogen invasion is not trivial. In more than half a million people in North America each year, this system fails and severe sepsis ensues, killing approximately one-third of these people. Therefore, understanding the behavior of the immune system in response to pathogens, particularly the role of neutrophils, is essential. There is much urgency in this regard, as antibiotic-resistant bacteria such as Staphylococcus aureus and multidrug-resistant Gram-negative bacilli are on the rise, and viruses (such as the SARS corona virus and H5N1 and H1N1 influenza viruses) that make the host more susceptible to secondary infections are also becoming more prominent. Tweaking host immunity may be a way to fight these emerging pathogens. In addition to the inflammation that occurs in blood vessels as a result of infection, inflammation can also occur intravascularly as a consequence of cell death or sterile injury. Whether the neutrophil can discriminate between a sterile injury and an infection is not clear, but the molecular mechanisms mediating neutrophil recruitment can be quite variable. Ultimately, to perform their functions, neutrophils need to know where to go. Therefore, efficient neutrophil guidance through the vasculature and into the affected tissue site is crucial and is normally governed by chemotactic gradients. During sys-temic infection, this system is altered, as the highest concentrations of chemokines and other chemotactic agents are found in plasma. This reverse chemotactic gradient results in activated neutrophils within the vasculature. For many years, the prevailing view was that these neutrophils get stuck in the capillary beds of lungs and liver where they release their cytotoxic contents, which induce inappropriate tissue injury leading to multiorgan failure. However, recently, other explanations have been put forth that suggest that sequestra-tion of neutrophils in lungs and liver is beneficial to host survival. New and somewhat unorthodox ways by which neutrophils may fight bacterial infections in the blood have been described. As one example, neutrophils have been shown to expel their DNA to form neutrophil extracellular traps (NETs) to ensnare bacteria before dying. Interactions between platelets and neutrophils are essential for this process to occur in the vasculature. This review discusses recent work pertaining to neutrophil recruitment and functions during both sterile injury and infectious stimuli. We use sepsis as an example of the war between neutrophils and bacteria and the intriguing approaches that are implemented as the host and pathogen each attempt to get the upper hand. We also discuss the emerging roles of neutrophils during tissue repair and angiogen-esis. Many of these discoveries rely on experimental mouse models of inflammation and newly evolving imaging technology, and we pay particular attention to these studies. However, it is noteworthy that the relevance of many of these observations in mice remains to be confirmed in humans. Neutrophil recruitment to sites of local infection Over the last few years, the multistep process of neutrophil recruitment from blood to tissue has been extensively studied using various in vivo microscopy approaches (summarized in Fig. 1). In vivo spinning-disk confocal, laser-scanning confocal and two-photon microscopy have enabled the refined, high-resolution examination of neutrophil behavior in the context of other cells and allowed researchers to follow the interactions of neutrophils with the surrounding endothelium and interendothelial junctions, as well as their behavior as they emigrate from the vasculature. Here we focus on how neutrophils have a key regulatory role in vascular inflammation. Recent studies using advanced imaging techniques have yielded new insights into the mechanisms by which neutrophils contribute to defense against bacterial infections and also against sterile injury. In these settings, neutrophils are recruited by various mechanisms depending on the situation. We also describe how these processes may be disrupted in systemic infections, with a particular emphasis on mouse models of sepsis. Neutrophils are often immobilized in the lungs and liver during systemic infections, and this immobilization may be a mechanism through which bacteria can evade the innate immune response or allow neutrophils to form neutrophil extracellular traps that trap and kill bacteria in blood. The platelet is also an important player in sepsis, and we describe how it collaborates with neutrophils in the formation of neutrophil extracellular traps.