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Antioxidant delivery may be targeted toward the alveolar epithelium by encapsulating superoxide dismutase (SOD) and catalase in liposomes made from pulmonary surfactant. We studied whether antioxidant-surfactant liposomes increase cellular antioxidant activity in alveolar type II cells and whether this effect is influenced by the presence of surfactant protein A (SP-A). Cu,Zn SOD and catalase were encapsulated in liposomes made from synthetic phospholipids with or without 5% SP-A or from natural cow surfactant. Alveolar type II cells from adult rats were preincubated for 20 h, and liposome mixtures were added for 24 h, followed by measurement of cellular SOD and catalase activities (U/mg DNA). Antioxidant-surfactant liposomes increased alveolar type II cell antioxidant activity sharply. Uptake of SOD/catalase from liposomes with synthetic phospholipids and SP-A was twice that from liposomes without SP-A and did not further improve in the presence of SP-B and -C. Encapsulation of antioxidants diminished the surface activity of the surfactant liposomes, but this feature was absent in the presence of SP-A. These data suggest that: 1) antioxidant-surfactant liposomes augment alveolar type II cell antioxidant activity, 2) liposomal uptake is facilitated by the presence of SP-A, and 3) inhibition of surface activity of surfactant by encapsulated antioxidants can be reversed by SP-A.