Oxidative stress is a common feature of obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD). Lung macrophages are key innate immune cells that can generate ...oxidants and are known to display aberrant polarization patterns and defective phagocytic responses in these diseases. Whether these characteristics are linked in one way or another and whether they contribute to the onset and severity of exacerbations in asthma and COPD remain poorly understood. Insight into oxidative stress, macrophages, and their interactions may be important in fully understanding acute worsening of lung disease. This review therefore highlights the current state of the art regarding the role of oxidative stress and macrophages in exacerbations of asthma and COPD. It shows that oxidative stress can attenuate macrophage function, which may result in impaired responses toward exacerbating triggers and may contribute to exaggerated inflammation in the airways.
The different faces of the macrophage in asthma van der Veen, T Anienke; de Groot, Linsey E S; Melgert, Barbro N
Current opinion in pulmonary medicine,
2020-January, Letnik:
26, Številka:
1
Journal Article
Odprti dostop
Asthma is a chronic inflammatory disease in which changes in macrophage polarization have been shown to contribute to the pathogenesis. The present review discusses the contribution of changes in ...macrophage function to asthma related to polarization changes and elaborates on possible therapeutic strategies targeting macrophage function and polarization.
Macrophage function alterations were shown to contribute to asthma pathology in several ways. One is by impaired phagocytosis and efferocytosis. Another is by changing inflammation, by altered (anti)inflammatory cytokine production and induction of the inflammasome. Finally, macrophages can contribute to remodeling in asthma, although little evidence is present in humans yet.Novel therapeutic strategies targeting macrophages include dampening inflammation by changing polarization or by inhibiting the NLRP3 inflammasome, and by targeting efferocytosis. However, many of these studies were performed in animal models leaving their translation to the clinic for future research.
The present review emphasizes the contribution of altered macrophage function to asthma, gives insight in possible new therapeutic strategies targeting macrophages, and indicates which knowledge gaps remain open.
Asthma is a heterogenous disease with different inflammatory subgroups that differ in disease severity. This disease variation is hampering treatment and development of new treatment strategies. ...Macrophages may contribute to asthma phenotypes by their ability to activate in different ways, i.e., T helper cell 1 (Th1)-associated, Th2-associated, or anti-inflammatory activation. It is currently unknown if these different types of activation correspond with specific inflammatory subgroups of asthma. We hypothesized that eosinophilic asthma would be characterized by having Th2-associated macrophages, whereas neutrophilic asthma would have Th1-associated macrophages and both having few anti-inflammatory macrophages. We quantified macrophage subsets in bronchial biopsies of asthma patients using interferon regulatory factor 5 (IRF5)/CD68 for Th1-associated macrophages, CD206/CD68 for Th2-associated macrophages and interleukin 10 (IL10)/CD68 for anti-inflammatory macrophages. Macrophage subset percentages were investigated in subgroups of asthma as defined by unsupervised clustering using neutrophil/eosinophil counts in sputum and tissue and forced expiratory volume in 1 s (FEV1). Asthma patients clustered into four subgroups: mixed-eosinophilic/neutrophilic, paucigranulocytic, neutrophilic with normal FEV1, and neutrophilic with low FEV1, the latter group consisting mainly of smokers. No differences were found for CD206+ macrophages within asthma subgroups. In contrast, IRF5+ macrophages were significantly higher and IL10+ macrophages lower in neutrophilic asthmatics with low FEV1 as compared to those with neutrophilic asthma and normal FEV1 or mixed-eosinophilic asthma. This study shows that neutrophilic asthma with low FEV1 is associated with high numbers of IRF5+, and low numbers of IL10+ macrophages, which may be the result of combined effects of smoking and having asthma.
Achieving reliably high production of reactive oxygen species (ROS) in photodynamic therapy (PDT) remains challenging. Graphene quantum dots (GQDs) hold great promise for PDT. However, the ...photochemical processes leading to GQD-derived ROS generation have not yet been fully elucidated.
Physicochemical characteristics of GQDs were comprehensively investigated, including electron paramagnetic resonance analysis of singlet oxygen production. Dark toxicity was assessed in vitro and in vivo.
GQDs demonstrated excellent photoluminescent features, corrosion resistance, high water solubility, high photo/pH-stability, in vitro and in vivo biocompatibility and very efficient singlet oxygen/ROS generation.
The enhanced ROS generation, combined with good biocompatibility and minimal toxicity in vitro and in vivo support the potential of GQDs for future PDT application.
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