Oxidative stress and macrophages: driving forces behind exacerbations of asthma and chronic obstructive pulmonary disease?

Abstract

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.

Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice

“…Asthma is an allergic inflammatory respiratory disease. Patients with chronic asthma continuously display chronic inflammation and oxidative stress [8]. Furthermore, pulmonary epithelial cells and immune cells are continuously activated, and they release various inflammatory cytokines, inflammatory mediators, and oxidative molecules that damage cells and tissues, which reduces lung function [6,29].…”

“…Previous studies pointed out that, in patients with asthma, the airways are stimulated to induce excessive oxidative stress, which aggravates mucus and sputum production and also damages lung cells [48,49]. Asthmatic mouse models and in vitro cellular experiments showed that allergens or inflammatory cytokines could stimulate airway epithelial cell activation, which increased chemokine release, attracted inflammatory immune cell infiltration into the lungs, and induced ROS production in tracheal epithelial cells [8,50]. Animal experiments also showed that these inflamed immune cells released high levels of inflammatory mediators in the lungs and induced oxidative stress, which damaged lung cells and attenuated lung function [51,52].…”

“…Hence, sesamol suppressed ROS release, and thus maintained lung function in asthmatic mice. We employed a lipid peroxidation assay to detect MDA activity, an identifying marker of oxidative stress in cells or tissues [8]. Additionally, glutathione is an important antioxidant enzyme that regulates oxidative stress in the lungs of patients with asthma [53].…”

“…In addition, inflammatory epithelial cells can stimulate the expression of oxidases, such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and inducible nitric oxide synthase, which produce reactive oxygen species (ROS) and nitric oxide. These conditions cause oxidative stress, which leads to airway remodeling, smooth muscle thickening, and pulmonary cell damage [8]. Therefore, in the airways, ROS and inflammatory response cytokines are dangerous signaling molecules that cause persistent respiratory cell damage and respiratory dysfunction.…”

Serum heme oxygenase-1 measurement is useful for evaluating disease activity and outcomes in patients with acute respiratory distress syndrome and acute exacerbation of interstitial lung disease

“…Nuclear factor-erythroid 2 p45 subunit-related factor 2 (Nrf2) is essential for activating response in the lung due to induction of the expression of antioxidant and these enzymes are expressed in bronchial and alveolar epithelial cells and macrophages of the lung (8). Several clinical evidences suggested that increased oxidative/nitrosative stress might play a major role in the progression of various lung diseases such as idiopathic pulmonary brosis (IPF), chronic obstructive pulmonary disease, and ARDS (9)(10)(11)(12)(13)(14). HO-1 catalyzes heme degradation to biliverdin-IXα, carbon monoxide, and iron.…”