title: Oxidative inactivation of alpha 1-proteinase inhibitor by alveolar epithelial type II cells.
abstract: 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.
authors.affiliation: Laboratoire de Pathologie Respiratoire Expérimentale et de Pollution Atmosphérique, Contrat Jeune Formation Institut National de la Santé et de la Recherche Médicale 90-06, Lille, France.
authors.forename: B
authors.initials: B
authors.lastname: Wallaert
authors.forename: C
authors.initials: C
authors.lastname: Aerts
authors.forename: B
authors.initials: B
authors.lastname: Gressier
authors.forename: P
authors.initials: P
authors.lastname: Gosset
authors.forename: C
authors.initials: C
authors.lastname: Voisin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000515:alpha 1-Antitrypsin; D013481:Superoxides; D006861:Hydrogen Peroxide; D010196:Pancreatic Elastase