Effects of pharmaceutical compounds on ciliary beating in human nasal epithelial cells: a comparative study of cell culture models.
OBJECTIVE
To test two in vitro human nasal epithelial cell culture systems for their ability to screen the effects of pharmaceutical compounds on ciliary beating.


METHODS
Human nasal epithelial cells were cultured as monolayer and in a sequential monolayer-suspension culture with in vitro ciliogenesis. The influence of reference cilio-stimulatory compounds (glycocholate, isoprenaline), reference cilio-inhibitory compounds (chlorocresol, diphenhydramine) and pH on ciliary beating was investigated using computerized microscope photometry.


RESULTS
Sodium glycocholate (0.5% w/v) maximally and reversibly increased CBF of the cells in both culture systems by 26 +/- 4% (monolayer) and 18 +/- 6% (suspension). Similarly, isoprenaline (10(-3) M) maximally, but irreversibly increased CBF of the cells by 14 +/-3% (monolayer) and 17 +/- 4% (suspension). Chlorocresol (0.005% w/ v) reversibly reduced the CBF of the cells by 50 +/- 6% (monolayer) and 34 +/- 4% (suspension); at a higher concentration (0.1% w/v) it resulted in instantaneous and irreversible ciliostasis. Diphenhydramine (0.1% w/v) reversibly reduced CBF in both culture systems by 45 +/- 13% (monolayer) and 69 +/- 5% (suspension); irreversible cilio-stasis occurred in less than 2 minutes in both culture systems upon cell exposure to diphenhydramine (1.0% w/v). In the monolayer culture system, CBF was stable only within the physiological pH range of 6.5-8.0; ciliary beating in the suspension culture remained stable within a pH range of 4.0-10.0.


CONCLUSIONS
Both cell culture systems are suitable for screening the effects of pharmaceutical compounds on ciliary beating. Especially the sequential monolayer-suspension culture appears to be very promising as ciliary activity can be preserved for as long as 6 months.
Agu
R U
RU
Laboratorium voor Faracotechnologie en Biofarmacie, K.U. Leuven, Belgium.
Jorissen
M
M
Willems
T
T
Van den Mooter
G
G
Kinget
R
R
Augustijns
P
P
D018926:Anti-Allergic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects* / Q000502:physiology; D003408:Cresols / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D005659:Fungicides, Industrial / Q000494:pharmacology; D006000:Glycocholic Acid / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D009296:Nasal Cavity / Q000166:cytology*; D010507:Periodicity; D013566:Sympathomimetics / Q000494:pharmacology
D018926:Anti-Allergic Agents; D002756:Cholagogues and Choleretics; D003408:Cresols; D005659:Fungicides, Industrial; D013566:Sympathomimetics; C006984:chlorocresol; D004155:Diphenhydramine; D006000:Glycocholic Acid; D007545:Isoproterenol