Pseudomonas pyocyanine alters calcium signaling in human airway epithelial cells.
Pseudomonas aeruginosa, an opportunistic human pathogen, causes both acute and chronic lung disease. P. aeruginosa exerts many of its pathophysiological effects by secreting virulence factors, including pyocyanine, a redox-active compound that increases intracellular oxidant stress. Because oxidant stress has been shown to affect cytosolic Ca2+ concentration ([Ca2+]c) in other cell types, we studied the effect of pyocyanine on [Ca2+]c in human airway epithelial cells (A549 and HBE). At lower concentrations, pyocyanine inhibits inositol 1,4,5-trisphosphate formation and [Ca2+]c increases in response to G protein-coupled receptor agonists. Conversely, at higher concentrations, pyocyanine itself increases [Ca2+]c. The pyocyanine-dependent [Ca2+]c increase appears to be oxidant dependent and to result from increased inositol trisphosphate and release of Ca2+ from intracellular stores. Ca2+ plays a central role in epithelial cell function, including regulation of ion transport, mucus secretion, and ciliary beat frequency. By disrupting Ca2+ homeostasis, pyocyanine could interfere with these critical functions and contribute to the pathophysiological effects observed in Pseudomonas-associated lung disease.
Denning
G M
GM
Department of Internal Medicine, Veterans Affairs Medical Center and The University of Iowa, Iowa City, Iowa, 52242, USA.
Railsback
M A
MA
Rasmussen
G T
GT
Cox
C D
CD
Britigan
B E
BE
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010084:Oxidation-Reduction; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D011710:Pyocyanine / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction
D011956:Receptors, Cell Surface; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D011710:Pyocyanine; D019204:GTP-Binding Proteins; D002118:Calcium