Aerosolization of superoxide dismutase. Augmentation of respiratory epithelial lining fluid antioxidant screen by aerosolization of recombinant human Cu++/Zn++ superoxide dismutase.
Various human pulmonary diseases are characterized by an increased oxidant burden on the respiratory epithelial surface. As a step toward developing a therapy to augment the antioxidant defenses of respiratory epithelial lining fluid (ELF) of the human lung, we have evaluated the feasibility of aerosolizing a human protein antioxidant to the respiratory epithelial surface of an experimental animal sufficiently large to permit repetitive sampling of ELF. To accomplish this, recombinant human Cu++/Zn++ superoxide dismutase (rSOD) was aerosolized to sheep, and the levels of human superoxide dismutase (SOD) and antisuperoxide anion (O2.-) capacity were quantified in ELF over time. In vitro aerosolization did not alter the specific activity of rSOD (p > 0.5). In vivo aerosolization of rSOD (100 mg) to sheep (n = 7) resulted in peak amounts of human Cu++/Zn++ SOD in ELF of 3.1 +/- 0.6 mumol/L, with a parallel increase in the anti-O2.- capacity of ELF. For the duration of the study (5 h), levels of SOD and anti-O2.- in ELF remained elevated, with a value 50 percent of the peak at 5 h. Aerosolization of phosphate-buffered saline (n = 5) had no effect on SOD or anti-O2.- levels in ELF. In animals receiving rSOD, there was no change in the specific activity of SOD recovered in ELF compared to the starting material (p > 0.4). We conclude that rSOD can be delivered by aerosol to the ELF of a large animal with preservation of specific activity and that a substantial increase in both the amount of SOD and the anti-O2.- capacity can be achieved for a period of time applicable to human therapy, supporting the rationale for evaluation of rSOD aerosol as an antioxidant in human pulmonary disease.
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
A
A
Gillissen
J H
JH
Roum
R F
RF
Hoyt
R G
RG
Crystal
D000336:Aerosols; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D011994:Recombinant Proteins / Q000008:administration & dosage; D012137:Respiratory System / Q000378:metabolism*; D012756:Sheep; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000336:Aerosols; D000975:Antioxidants; D011994:Recombinant Proteins; D013481:Superoxides; D013482:Superoxide Dismutase