.) Pulmonary surfactant is a complex that reduces surface tension at the air-liquid interface and plays a crucial role in neonatal adaptation. A lack of surfactant, usually due to immaturity of the lung, leads to decreased pulmonary compliance and respiratory distress. The mainstay in the management of respiratory distress is oxygen and respiratory support. Oxidative injury from the treatment itself can lead to further pulmonary disease. The intracellular pool of glutathione provides protection against such injury because of its role in reduction of lipid peroxides, inhibition of free radical processes, and the removal of reactive electrophiles. Dr. Jones has found that pulmonary alveolar type II cells from adult and neonatal animals have a Na+-dependent transport system. This transport was demonstrated in healthy type II cells and the transport was demonstrated to be against a glutathione concentration gradient. This transport mechanism then allowed these cells to utilize exogenous glutathione for protection against oxidative injury. This protection by exogenous glutathione was in addition to that provided by endogenous pools of glutathione. The preliminary data have demonstrated that the lung can transport supplemental glutathione from the vasculature to the alveolar surface when ventilated under hyperoxic conditions. The purpose of this proposal is to characterize further the glutathione transport mechanisms that are involved in protection by exogenous glutathione. This will entail: 1) characterization of the mechanisms regulating glutathione transport by the alveolar type II cell, 2) examination of this transport system in plasma membrane vesicles obtained from alveolar type II cells and 3) isolation of the transporter as a prelude to studies of its properties and mechanism. The purification of the transporter will then be used for preparation of antibodies for investigations of the molecular biology of this system. The results of these studies may provide knowledge about pulmonary glutathione uptake and its function in protection against oxidative injury in alveolar type II cells.
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