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Oxidant stress in asthma
  1. Ryszard Dworski
  1. Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
  1. Dr R Dworskiryszard.dworski{at}mcmail.vanderbilt.edu

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Asthma is a chronic inflammatory disease of the respiratory tract of unknown aetiology. In severe asthma airway diathesis is profound, and thus apparent. Recently, however, evidence has indicated that specific inflammatory abnormalities exist even in the airways of subjects with mild disease. As inflammation is often associated with an increased generation of reactive oxygen species (ROS), and the biochemical environment in the asthmatic airways is favourable for free radical mediated reactions, it is rational to surmise that an oxidant stress could be mechanistically important in asthma.

Cellular and biochemical sources of ROS in asthma

The inflammatory cells recruited to the asthmatic airways have an exceptional capability for producing ROS. Activated eosinophils, neutrophils, monocytes, and macrophages can generate superoxide (O2 ) via the membrane associated NADPH-dependent complex. Subsequently, dismutation of O2 gives hydrogen peroxide (H2O2). O2 and H2O2 per se are moderate oxidants; however, both species are critical for the formation of potent cytotoxic radicals in biological systems through their interaction with other molecules. For example, hydroxyl radical (OH), a powerful and indiscriminate oxidant, can be produced from O2 and hypohalous acids (HOCl or HOBr). The latter component can be formed from H2O2 and a halide (Cl or Br) in a reaction catalysed by myeloperoxidase (MPO) provided by neutrophils and monocytes,1 or eosinophil peroxidase (EPO) from eosinophils.2 MPO preferably utilises Cl as a halide, whereas EPO uniquely prefers Br. Moreover, a recent study has shown that MPO and EPO can use nitrite (a major end product of nitric oxide (NO) metabolism) and H2O2 as substrates to promote formation of reactive nitrating intermediates.3 The oxidative injury caused by eosinophils can be substantial because the cells possess several times greater capacity to …

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