These results indicate that after ASCC there is a release of MPO. Our study suggests that immunotherapy actively modifies the release of MPO after ASCC.
Inhaled corticosteroids (ICSs) are widely used in chronic obstructive pulmonary disease (COPD) and in combination with long-acting β2 agonists (LABAs) to reduce exacerbations and improve patient lung function and quality of life. However, ICSs have been associated with an increased risk of pneumonia in individuals with COPD, although the magnitude of this risk remains unclear. Therefore, it is difficult to make informed clinical decisions that balance the benefits and adverse effects of ICSs in people with COPD. There may be other causes of pneumonia in patients with COPD, and these causes are not always considered in studies on the risks of using ICSs in COPD. We consider it very useful to clarify these aspects in assessing the influence of ICSs on the incidence of pneumonia and their role in the treatment of COPD. This issue has important implications for current practice and the evaluation and management of COPD, since COPD patients may benefit from specific ICS-based treatment strategies. Many of the potential causes of pneumonia in patients with COPD can act synergistically, so they can be included in more than one section.
BackgroundNeutrophils are involved in the pathophysiology of allergic asthma, where the Eosinophil Cationic Protein (ECP) is a critical inflammatory mediator. Although ECP production is attributed to eosinophils, we reported that ECP is also present in neutrophils from allergic patients where, in contrast to eosinophils, it is produced in an IgE-dependent manner. Given the key role of ECP in asthma, we investigated the molecular mechanisms involved in ECP production as well as the effects induced by agonists and widely used clinical approaches. We also analyzed the correlation between ECP production and lung function.MethodsNeutrophils from allergic asthmatic patients were challenged with allergens, alone or in combination with cytokines, in the presence of cell-signaling inhibitors and clinical drugs. We analyzed ECP levels by ELISA and confocal microscopy. Lung function was assessed by spirometry.ResultsIgE-mediated ECP release is dependent on phosphoinositide 3-kinase, the extracellular signal-regulated kinase (ERK1/2) and the production of reactive oxygen species by NADPH-oxidase. Calcineurin phosphatase and the transcription factor NFAT are also involved. ECP release is enhanced by the cytokines interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor, and inhibited by interferon-γ, IL-10, clinical drugs (formoterol, tiotropium and budesonide) and allergen-specific IT. We also found an inverse correlation between asthma severity and ECP levels.ConclusionsOur results suggest the molecular pathways involved in ECP production and potential therapeutic targets. We also provide a new method to evaluate disease severity in asthmatic patients based on the quantification of in vitro ECP production by peripheral neutrophils.
BackgroundDespite the evidence that Lactoferrin (Lf) is involved in allergic asthma processes, it is unknown whether neutrophils can be one of the main cellular sources of this key inflammatory mediator directly in response of an IgE mediated stimulus. The present study was undertaken to analyze this question.MethodsNeutrophils from healthy subjects (n = 34) and neutrophils from allergic asthmatic patients (n = 102) were challenged in vitro with specific allergens to which the patients were sensitized, PAF, or agonist mAbs against IgE-receptors, and the levels of Lf were measured in the culture supernatant. The levels of serum IgE together with the severity of symptoms were also analyzed.ResultsLf was released into the culture supernatant of neutrophils from allergic asthmatic patients in response to allergens and PAF. This response was highly allergen-specific, and did not happen in neutrophils from healthy donors. Allergen effect was mimicked by Abs against FcεRI and galectin-3 but not by FcεRII. The levels of released Lf correlated well with the levels of serum specific IgE and severity of asthma symptoms. These observations represent a novel view of neutrophils as an important source of Lf in allergic asthma. Importantly, the levels of released Lf by neutrophils could therefore be used to evaluate disease severity in allergic asthmatic patients.
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