Oxidative inactivation of alpha 1-proteinase inhibitor by alveolar epithelial type II cells.

The aim of this work was to evaluate the ability of guinea pig alveolar epithelial type II cells to generate significant amounts of reactive oxygen species to inactivate alpha 1-proteinase inhibitor (alpha 1-PI). Inactivation of alpha 1-PI was evaluated by its inhibitory activity against porcine pancreatic elastase and was expressed as a percentage. The same experiments were performed in parallel with alveolar macrophages (AM) obtained from the same animals and with MRC-5 fibroblasts. Both type II cells and AM released significant amounts of hydrogen peroxide and superoxide, whereas the fibroblasts did not. Unstimulated type II cells (0.5 +/- 2%), AM (1.2 +/- 1.5%), and fibroblasts (0.5 +/- 0.5%) were unable to inactivate alpha 1-PI. Addition of phorbol myristate acetate did not increase their ability to inactivate alpha 1-PI. In contrast, type II cells (79.7 +/- 7%) and AM (80.1 +/- 8%) dramatically inactivated alpha 1-PI in the presence of myeloperoxidase (25 mU/ml), whereas fibroblasts did not. Addition of catalase to the reaction significantly prevented the inactivation of alpha 1-PI. Western blot analysis of alpha 1-PI did not reveal a significant proteolysis of alpha 1-PI, which supports the hypothesis that, in the presence of neutrophil-derived myeloperoxidase, type II cells may oxidatively inactivate alpha 1-PI.