PSEUDOMONAS PYOCYANINE ALTERS CALCIUM SIGNALING IN HUMAN AIRWAY EPITHELIAL-CELLS

Pseudomonas aeruginosa, an opportunistic human pathogen, causes both a cute and chronic lung disease. P. aeruginosa exerts many of its pathop hysiological effects by secreting virulence factors, including pyocyan ine, a redox-active compound that increases intracellular oxidant stre ss. Because oxidant stress has been shown to affect cytosolic Ca2+ con centration ([Ca2+](c)) in other cell types, we studied the effect of p yocyanine on [Ca2+](c) in human airway epithelial cells (A549 and HBE) . At lower concentrations, pyocyanine inhibits inositol 1,4,5-trisphos phate formation and [Ca2+](c) increases in response to G protein-coupl ed receptor agonists. Conversely, at higher concentrations, pyocyanine itself increases [Ca2+](c). The pyocyanine-dependent [Ca2+](c) increa se appears to be oxidant dependent and to result from increased inosit ol trisphosphate and release of Ca2+ from intracellular stores. Ca2+ p lays a central role in epithelial cell function, including regulation of ion transport, mucus secretion, and ciliary beat frequency. By disr upting Ca2+ homeostasis, pyocyanine could interfere with these critica l functions and contribute to the pathophysiological effects observed in Pseudomonas-associated lung disease.