title: Rotation frequency of human bronchial and nasal epithelial spheroids as an indicator of mucociliary function.
abstract: 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
  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 degrees C, there was a temperature-dependent increase: RF(27)( degrees )(C) = 0.27 +/- 0.08 s(-1), and RF(37)( 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.
authors.affiliation: Division of Pneumology, Department of Internal Medicine, University Hospital, Ludwig Maximilian University, Munich, Germany. gamarra@med.uni-muenchen.de
authors.forename: Fernando
authors.initials: F
authors.lastname: Gamarra
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bergner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stauss
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stocker
authors.forename: Stefan
authors.initials: S
authors.lastname: Grundler
authors.forename: Rudolf Maria
authors.initials: RM
authors.lastname: Huber
mesh_terms: D001993:Bronchodilator Agents / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009079:Mucociliary Clearance / Q000187:drug effects / Q000502:physiology*; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D012399:Rotation; D018874:Spheroids, Cellular / Q000187:drug effects / Q000502:physiology*; D013696:Temperature; D013997:Time Factors
chemical_list: D001993:Bronchodilator Agents; D007545:Isoproterenol