Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients

Abstract

Bronchial asthma is a chronic inflammatory disease of the airways characterized by an increased recruitment of inflammatory cells, including mononuclear phagocytic cells such as monocytes [1]. The ability of these cells to generate highly reactive oxygen species (ROS), including super-oxide anion, following activation of a membraneassociated reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important part of the host defence system, and has also been implicated in inflammation in a variety of pulmonary diseases [2,3], including asthma [4,5]. Oxygen metabolites cause tissue injury, smooth muscle contraction, increased airway vascular permeability, and may increase airway responsiveness and release of var-ious mediators [4].In previous studies, it has been shown that alveolar macrophages [6], blood monocytes [5] and eosinophils [7] from asthmatic patients were able to produce high amounts of ROS. Alveolar macrophage activation was correlated with the severity of asthma [6]. This activation occurred immediately after antigen challenge, and the appearance of high-density macrophages which release higher amounts of superoxide anion occurred during the late airway response [8]. Several investigators have also suggested that polymorphonuclear leucocytes from asthmatic patients generated more ROS than control subjects [9,10]. This activation was correlated with the level of bronchial hyperreactivity [11].Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma [12], but little is known about their molecular mechanism of action in improving symptoms or the way they reduce hyperresponsiveness. It has been proposed that corticosteroids inhibit the inflammatory process by redirection of lymphocyte traffic, inhibition of cytokine gene expression [13] and inhibition of the expression of adhesion molecules [14].The effect of anti-inflammatory corticosteroids on oxygen radical production by phagocytes has been less extensively studied, and the results are contradictory. In vitro studies have demonstrated an inhibitory effect of high corticosteroid concentrations on oxygen radical production in human granulocytes [15]. In contrast, dexamethasone treatment has been reported to have no effect on ROS secretion in human blood-derived macrophages [16], but have a stimulatory effect on human monocytes [17]. It has been reported that in vivo corticosterone had no effect on murine peritoneal inflammatory cells [18]. Ex vivo inhaled steroid treatment had no effect on superoxide anion production in human alveolar macrophages [19,20]. In contrast, a recent study showed that in vivo administration of dexamethasone or methylprednisolone led to a dose-dependent inhibition of rat peritoneal leucocyte chemiluminescence [21]. Moreover, hydrocortisone was found to inhibit superoxide anion production during an asthma attack [22].Superoxide anion production by monocytes of corticosteroid-treated asthmatic patients. M. Majori, I. Vachier, P. Godard, M. Farce, J. Bousquet, P. Chanez. ...

Alterations of Erythrocyte Superoxide Dismutase activity in patients suffering from asthma attacks

“…Previous studies have shown that treatment with corticosteroids reduces oxidative stress and restores intracellular SOD activity levels in mild asthma [28,29]. In our study, no correlation between inhaled steroids and SOD activity was found and complements the findings of a previous study [15], thus making it less likely that inhaled steroids influence SOD activity.…”

Glucocorticoid receptor-binding characteristics in severe asthma

“…Whole cell-binding assay PBM were isolated from blood by centrifugation over isotonic Percoll solutions (Pharmacia, St. Quentin en Yvelines, France) as described previously [11]. Cell viability and number were determined using the trypan blue exclusion test.…”

Thiol Antioxidants Inhibit the Adjuvant Effects of Aerosolized Diesel Exhaust Particles in a Murine Model for Ovalbumin Sensitization

“…These studies were reproduced in large animals, where it was demonstrated that oxygen radicals contribute to Ag-induced airway hyperreactivity (35,36). In addition, neutrophils and mononuclear cells generate proportionately more O 2 Ϫ ⅐ and H 2 O 2 in the lungs of asthmatics compared with healthy controls (32,34). ROS generation also correlates with increased airway hyperreactivity in asthmatic lungs (31,33).…”