Pneumonia is a typical symptom of COVID-19 infection, while acute respiratory distress syndrome (ARDS) and multiple organ failure are common in severe COVID-19 patients
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NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond - PMC - 0 views
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SARS-CoV-2 infection has also been linked to increased neutrophil-to-lymphocyte ratios, which is associated with disease severity and clinical prognosis
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NETosis is a special form of programmed cell death in neutrophils, which is characterized by the extrusion of DNA, histones, and antimicrobial proteins in a web-like structure known as neutrophil extracellular traps (NETs)
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increased generation of reactive oxygen species (ROS) is a crucial intracellular process that causes NETosis
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NETs are important for preventing pathogen invasion, their excessive formation can result in a slew of negative consequences, such as autoimmune inflammation and tissue damage
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In COVID-19, major NET protein cargos of NETs (i.e., NE, MPO, and histones) are significantly elevated.
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SARS-CoV-2 can also infect host cells through noncanonical receptors such as C-type lectin receptors
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Immunopathological manifestations, including cytokine storms and impaired adaptive immunity, are the primary drivers behind COVID-19, with neutrophil infiltration being suggested as a significant cause
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NETosis, leading to aberrant immunity such as cytokine storms, autoimmune disorders, and immunosuppression.
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SARS-CoV-2 and its components (e.g., spike proteins and viral RNA) attach to platelets and increase their activation and aggregation in COVID-19, resulting in vascular injury and thrombosis, both of which are linked to NET formation
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early bacterial coinfections were more prevalent in COVID-19 patients than those infected with other viruses
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NETosis and NETs may also have a role in the development of post COVID-19 syndromes, including lung fibrosis, neurological disorders, tumor growth, and worsening of concomitant disease
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NETs and other by-products of NETosis have been shown to act as direct inflammation amplifiers. Hyperinflammation
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SARS-CoV-2 drives NETosis and NET formation to allow for the release of free DNA and by-products (e.g., elastases and histones). This may trigger surrounding macrophages and endothelial cells to secrete excessive proinflammatory cytokines and chemokines, which, in turn, enhance NET formation and form a positive feedback of cytokine storms in COVID-19
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NET release enables self-antigen exposure and autoantibody production, thereby increasing the autoinflammatory response
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patients with COVID-19 who have higher anti-NET antibodies are more likely to be detected with positive autoantibodies [e.g., antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA)]
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can enhance this process by interacting with neutrophils through toll-like receptor 4 (TLR4), platelet factor 4 (PF4), and extracellular vesicle-dependent processes
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have weakened adaptive immunity as well as a high level of inflammation
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tumor-associated NETosis and NETs promote an immunosuppressive environment in which anti-tumor immunity is compromised
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Following initial onset of COVID-19, an estimated 50% or more of COVID-19 survivors may develop multi-organ problems (e.g., pulmonary dysfunction and neurologic impairment) or have worsening concomitant chronic illness
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NETs in the bronchoalveolar lavage fluid of severe COVID-19 patients cause EMT in lung epithelial cells
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decreased E-cadherin (an epithelial marker) expression
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Patients with tumors have been shown to be more vulnerable to SARS-CoV-2 infection and subsequent development of severe COVID-19
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patients who have recovered from COVID-19 may have an increased risk of developing cancer or of cancer progression and metastasis
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vitamin C has been tested in phase 2 clinical trials aimed at reducing COVID-19-associated mortality by reducing excessive activation of the inflammatory response
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vitamin C is an antioxidant that significantly attenuates PMA-induced NETosis in healthy neutrophils by scavenging ROS
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Interleukin‐2 enhances the natural killer cell response to Herceptin‐coated H... - 1 views
onlinelibrary.wiley.com/...%3AAID-IMMU3016%3E3.0.CO%3B2-J
IL-2 breast cancer cancer NK cells HER-2 immunotherapy
shared by Nathan Goodyear on 18 Jun 18
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administration of low‐dose IL‐2 results in expansion of a CD3– / CD56+ NK cell population in patients with advanced cancer
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In breast cancer, Her2 / neu overexpression is associated with a worse histologicalgrade, decreased relapse‐free and overall survival periods, and altered sensitivity to chemotherapeutic regimens
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treatment with various concentrations of IL‐2 in vivo may induce distinct functions within the NK cell compartment and, therefore, may have profound effects on NK cell‐mediated cytotoxicity
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We show here that ADCC conducted by NK cells in vitro is enhanced by IL‐2 activation and is critically dependent on interactions between FcγRIII on NK cells and Herceptin‐coated tumor targets
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administration of low‐dose IL‐2 to patients results in the marked expansion of a CD56+ population of immune effectors with the ability to lyse antibody‐coated cancer targets
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NK cells represented only 7 % of lymphocytes prior to therapy but comprised over 50 % of the population after 10 weeks of low‐dose IL‐2
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These data suggest that the enhanced ADCC seen following the expansion of NK cells with low‐dose IL‐2 is likely due to an increase in the overall number of NK cells
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Stimulation of NK cells with IL‐2 resulted in a significant increase in the lysis of rhu4D5‐coated targets
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We have shown that costimulation with IL‐2 plus rhu4D5 results in significant production of IFN‐γ by NK cells with concomitant up‐regulation of cell‐surface activation and adhesion molecules
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It has been previously demonstrated that continuous low‐dose IL‐2 can expand a CD56+ lymphocyte population, and we have now shown that this cell population is a potent mediator of ADCC against rhu4D5 mAb‐coated Her2 / neu+ targets
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These results suggest that administration of low‐dose IL‐2 can be used to expand NK cell numbers, while higher doses may be used to enhance their cytolytic capacity in the setting of mAb therapy
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we have demonstrated that NK cell lysis of Her2 / neu+ breast cancer cell lines in the presence of rhu4D5 mAb is markedly enhanced following stimulation with IL‐2
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we have presented evidence that administration of low‐dose IL‐2 in vivo results in the expansion of a potent NK cell effector population
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Our experiments suggest that NK cells costimulated with IL‐2 and immobilized IgG can secrete potent immunomodulatory cytokines which may serve to potentiate the anti‐tumor immune response.