Open AccessEchinocandins Accelerate Particle Transport Velocity in the Murine Tracheal Epithelium: Dependency on Intracellular Ca 2+ Stores
Author(s) -
Sabrina Müller,
Maximilian Carl Droll,
Christian Koch,
Sebastian Weiterer,
Markus A. Weigand,
Michael Sander,
Michael Henrich
Publication year - 2021
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00669-21
Subject(s) - anidulafungin , echinocandin , echinocandins , endoplasmic reticulum , intracellular , micafungin , caspofungin , biophysics , cytosol , mucociliary clearance , biology , microbiology and biotechnology , chemistry , pharmacology , biochemistry , medicine , enzyme , lung , voriconazole , antifungal , fluconazole
The mucociliary clearance of lower airways is modulated by different physiologic stimuli and also by pathophysiologic agents like polluting substances or pharmaceutical molecules. In the present investigation, we measured the particle transport velocity (PTV) of mouse tracheae as a surrogate for mucociliary clearance. In mouse tracheal preparations, we detected a sustained increase in the PTV under the application of the echinocandins caspofungin, anidulafungin, and micafungin. In further experiments, we observed the effects of echinocandins on the PTV were dependent on intracellular Ca 2+ homeostasis. In Ca 2+ -free buffer solutions, the amplitude of the echinocandin-evoked rise in the PTV was significantly reduced relative to that in the experiments in Ca 2+ -containing solutions. Depletion of intracellular Ca 2+ stores of the endoplasmic reticulum (ER) by caffeine completely prevented an increase in the PTV with subsequent caspofungin applications. Mitochondrial Ca 2+ stores seemed to be unaffected by echinocandin treatment. We also observed no altered generation of reactive oxygen species under the application of echinocandins as probable mediators of the PTV. Consequently, the observed echinocandin effects on the PTV depend upon the Ca 2+ influx and Ca 2+ contents of the ER. We assume that all three echinocandins act intracellularly on ER Ca 2+ stores to activate Ca 2+ -dependent signal transduction cascades, enhancing the PTV.