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

L.E Marçal,P.E Newburger,J Rehder,A Condino-Neto

doi:10.1590/s0100-879x2004001100003

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.

Highlights

The major characteristics of asthma are reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation [1]
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
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)

Summary

Introduction

The major characteristics of asthma are reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation [1] This is a complex inflammatory disease that involves leukocytes, airway epithelial and smooth muscle cells, and several inflammatory mediators with multiple effects. Resident or infiltrating inflammatory phagocytes in the airways release reactive oxygen species and other mediators with pleiotropic effects [1]. The role of phagocytes in the pathophysiology of asthma is not completely understood They release enzymes, including extracellular matrix-degrading proteases, elastase, cytokines, and reactive oxygen species, which have been implicated in lung injury [3]. The reported effects of reactive oxygen species in asthma include a decrease of betaadrenergic function in lungs, airway smooth muscle contraction, increased vascular permeability, bronchial hyperresponsiveness, increased mucus secretion, impaired ciliary activity, generation of chemotactic factors, lipid peroxidation, and secondary production of mediators with a bronchoconstrictor effect [4,5]. SubseBraz J Med Biol Res 37(11) 2004 quent lung injury and more inflammation may take place

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