Superoxide release and cellular gluthatione peroxidase activity in leukocytes from children with persistent asthma

Abstract

Asthma is an inflammatory condition characterized by the involvement of several mediators, including reactive oxygen species. The aim of the present study was to investigate the superoxide release and cellular glutathione peroxidase (cGPx) activity in peripheral blood granulocytes and monocytes from children and adolescents with atopic asthma. Forty-four patients were selected and classified as having intermittent or persistent asthma (mild, moderate or severe). The spontaneous or phorbol myristate acetate (PMA, 30 nM)-induced superoxide release by granulocytes and monocytes was determined at 0, 5, 15, and 25 min. cGPx activity was assayed spectrophotometrically. The spontaneous superoxide release by granulocytes from patients with mild (N = 15), moderate (N = 12) or severe (N = 6) asthma was higher at 25 min compared to healthy individuals (N = 28, P < 0.05, Duncan test). The PMA-induced superoxide release by granulocytes from patients with moderate (N = 12) or severe (N = 6) asthma was higher at 15 and 25 min compared to healthy individuals (N = 28, P < 0.05 in both times of incubation, Duncan test). The spontaneous or PMA-induced superoxide release by monocytes from asthmatic patients was similar to healthy individuals (P > 0.05 in all times of incubation, Duncan test). cGPx activity of granulocytes and monocytes from patients with persistent asthma (N = 20) was also similar to healthy individuals (N = 10, P > 0.05, Kruskal-Wallis test). We conclude that, under specific circumstances, granulocytes from children with persistent asthma present a higher respiratory burst activity compared to healthy individuals. These findings indicate a risk of oxidative stress, phagocyte auto-oxidation, and the subsequent release of intracellular toxic oxidants and enzymes, leading to additional inflammation and lung damage in asthmatic children.

Cytological damage of nasal epithelium associated with decreased glutathione peroxidase in residents from a heavily polluted city

“…Thus, oxidative stress is a relevant risk factor for lung damage in chronic inXammatory diseases (Marcal et al 2004). …”

“…This inhibition can occur through the activation of endogenous antioxidants, as the glutathione peroxidase (GPX)/glutathione reductase system, which neutralizes the action of already formed free radicals. GPX reduces peroxidases and hydroperoxidases impacting on the cardiovascular system and respiratory tract, since oxidative stress can harm diVerent epithelia (like the nasal epithelium) when free radicals increase (Marcal et al 2004).…”

Aberrant function of neutrophils in asthma

“…Neutrophils recruited by allergen challenge generate sustained ROS in the airways, which may promote allergic inflammation through ROS generation [26] . The effects of reactive oxygen species in asthma include decreased beta-adrenergic function in lungs, airway smooth muscle contraction, increased vascular permeability, bronchial hyperresponsiveness, increased mucus secretion, impaired ciliary activity, generation of chemotactic factors and lipid peroxidation, and secondary production of mediators with a bronchoconstrictor effect [27] . It has been demonstrated that neutrophils purified from bronchoalveolarlavage fluid and peripheral blood from patients with allergic asthma released significantly higher quantities of ROS compared to healthy individuals [13,19,[27][28][29] .…”

“…The effects of reactive oxygen species in asthma include decreased beta-adrenergic function in lungs, airway smooth muscle contraction, increased vascular permeability, bronchial hyperresponsiveness, increased mucus secretion, impaired ciliary activity, generation of chemotactic factors and lipid peroxidation, and secondary production of mediators with a bronchoconstrictor effect [27] . It has been demonstrated that neutrophils purified from bronchoalveolarlavage fluid and peripheral blood from patients with allergic asthma released significantly higher quantities of ROS compared to healthy individuals [13,19,[27][28][29] . In mice mode of asthma, the gp91phox deficiency mice, the dominant superoxide generating enzyme in neutrophils, had decreased ROS production, and attenuated allergic inflammatory response to allergen challenge [30] .…”

The Role of Neutr Ophils and Their Apoptosis in There Solution of Inflammation

“…Oxidative stress, with decreased levels of superoxide dismutase, catalase and glutathione peroxidase, as indicators of exhausted antioxidant reserve capacity, often develops in sickly children, irrespective of the location of the inflammation process in the respiratory tract [20]. The increased lipid peroxidation against the background of antioxidant enzymes inhibition was detected in infants with severe pertussis, and bronchoobstructive diseases and can lead to some immune system disorders [21].…”