Determination of oxidized alpha-1-proteinase inhibitor in serum

Abstract

When alpha-1-PI is oxidized, it loses its ability to inhibit porcine elastase, although it retains its TIC. Therefore the ratio of TIC to EIC increases in proportion to the degree of oxidation of the inhibitor. We have developed a rapid procedure for determining the percentage of oxidized alpha-1-PI in plasma or serum based on the ratio of TIC to EIC of alpha-1-PI in these tissues. The TIC/EIC ratio is not influenced by the other proteins in serum nor by the concentration of alpha-1-PI. When this technique was adapted to measure to proportion of oxidized alpha-1-PI in the serum of young adult, healthy smokers and nonsmokers, 23% oxidized inhibitor was found in the smokers' sera, whereas no oxidized alpha-1-PI was detectable in sera of nonsmokers. Thus smoking leads to oxidation damage to circulating alpha-1-PI. Reduction of the EIC of the alpha-1-PI in the serum of smokers was compensated by a 1.43-fold increase in their serum alpha-1-PI titers; however, these data do not exclude the possibility of local depletion of the absolute EIC in the extravascular space of the lungs. This assay for oxidized alpha-1-PI may be useful in studies of the relationship between oxidation of alpha-1-PI and the development of pulmonary emphysema.