Rotation frequency of human bronchial and nasal epithelial spheroids as an indicator of mucociliary function

Background: We evaluated a new in vitro model for mucociliary
transport function. Spheroids of human respiratory epithelium show
beating cilia at their surface. When cultured in their own mucus,
spheroids can rotate along their axis due to coordinated ciliary
beating. Objective and Methods: To assess whether this setup yields
meaningful results we measured rotation frequency (RF) of human
bronchial or nasal epithelial spheroids under different
temperatures and concentrations of isoproterenol. Isoproterenol was
administered either as caged compound releasing active
isoproterenol after illumination with UV light, or through a
permeable membrane in a two-chamber system. Results: Under stable
conditions, RF remained constant over 200 min. Between 27 and 35 C,
there was a temperature-dependent increase: RF27 degrees C = 0.27
+/- 0.08 s(-1), and RF37 degrees C = 0.43 +/- 0.10 s(-1) (means +/-
SEM). Isoproterenol (10(-5), 10(-4) and 10(-3) mmol/l) induced
concentration-dependent increases in RF (9, 20 and 25%,
respectively; medians) if applied in the two-chamber system. The
experiments with caged isoproterenol did not yield conclusive
results, probably because the byproducts from photolysis negatively
affected ciliary function. The transport velocity at the surface of
bronchial and nasal spheroids was estimated to be 2.96 and 3.62
mm/min (medians), respectively, which is in the same range as mucus
transport velocity measured in vivo in humans. Conclusions: This
setup can be used to study mucociliary transport function under
controlled conditions in vitro, in particular as RF is likely to
reflect not only ciliary beat frequency, but also the coordination
of ciliary beating and the properties of the mucus. Copyright (C)
2006 S. Karger AG, Basel.