AUGMENTATION OF OXIDANT INJURY TO HUMAN PULMONARY EPITHELIAL-CELLS BYTHE PSEUDOMONAS-AERUGINOSA SIDEROPHORE PYOCHELIN

Pseudomonas aeruginosa causes acute and chronic infections of the huma n lung, with resultant tissue injury, We have previously shown that ir on bound to pyochelin, a siderophore secreted by the organism to acqui re iron, is an efficient catalyst for hydroxyl radical (HO.) formation and augments injury to pulmonary artery endothelial cells resulting f rom their exposure to superoxide (O-2(-.)) and/or H2O2. Sources for O- 2(-.) and H2O2 included phorbol myristate acetate (PMA)-stimulated neu trophils and pyocyanin, Pyocyanin, another P. aeruginosa secretory pro duct, undergoes cell-mediated redox, thereby forming O-2(-.) and H2O2. In P. aeruginosa lung infections, damage to airway epithelial cells i s probably more extensive than that to endothelial cells, Therefore, w e examined whether ferripyochelin also augments oxidant-mediated damag e to airway epithelial cells, A549 cells, a human type II alveolar epi thelial cell line, was exposed to H2O2, PMA-stimulated neutrophils, or pyocyanin, and injury was determined by release of Cr-51 from prelabe led cells. Ferripyochelin significantly increased (> 10-fold) oxidant- mediated cell injury regardless of whether H,O,, neutrophils, or pyocy anin was employed, Apo-pyochelin was not effective, and ferripyochelin was not toxic by itself at the concentrations employed, Spin trapping with pha-(4-pyrridyl-1-oxide)-N-t-butyl-nitrone-ethanol confirmed the generation of HO., and injury was decreased by a variety of antioxida nts, including superoxide dismutase, catalase, and dimethylthiourea, T hese data are consistent with the hypothesis that the presence of ferr ipyochelin at sites of P. aeruginosa lung infection could contribute t o tissue injury through its ability to promote HO.-mediated damage to airway epithelial cells.