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.