Pseudomonas siderophore pyochelin enhances neutrophil-mediated endothelial cell injury.
Pyochelin, a siderophore secreted by Pseudomonas aeruginosa, binds iron in a form which can catalyze the formation of hydroxyl radical (.OH) from neutrophil-derived superoxide (O2-.) and hydrogen peroxide (H2O2). Ferripyochelin induced a concentration-dependent increase in endothelial cell injury (51Cr release) resulting from exposure to H2O2, a xanthine/xanthine oxidase O2-./H2O2 generating system, or stimulated neutrophils. This process was dependent on the presence of iron. Formation of .OH was confirmed using spin trapping. Although a slight (13%) increase in neutrophil O2-. production in the presence of ferripyochelin was observed, this did not appear to account for the extent of endothelial cell injury observed. The antioxidants dimethylthiourea and catalase decreased endothelial cell injury, whereas dimethyl sulfoxide and superoxide dismutase were without effect. Fe-nitrilotriacetic acid and Fe-EDTA, which are also .OH catalysts, did not augment endothelial cell injury resulting from exposure to the above oxidant systems. In contrast to results with the endothelial cells, killing of P. aeruginosa by O2-./H2O2 derived from the reaction of xanthine and xanthine oxidase was not increased by ferripyochelin. These data are consistent with the possibility that the interaction of Pseudomonas- and phagocyte-derived secretory products could contribute to local tissue injury at sites of P. aeruginosa infection by causing the generation of .OH.
Britigan
B E
BE
Research Service, Veterans Affairs Medical Center, Iowa City, Iowa.
Rasmussen
G T
GT
Cox
C D
CD
D000818:Animals; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D017262:Siderophores / Q000378:metabolism*; D013481:Superoxides / Q000494:pharmacology; D013552:Swine; D013844:Thiazoles
D007502:Iron Chelating Agents; D010636:Phenols; D017262:Siderophores; D013844:Thiazoles; C025315:ferripyochelin; D013481:Superoxides; D017665:Hydroxyl Radical; C025316:pyochelin; D006861:Hydrogen Peroxide