Ru. Agu et al., Effects of pharmaceutical compounds on ciliary beating in human nasal epithelial cells: A comparative study of cell culture models, PHARM RES, 16(9), 1999, pp. 1380-1385
Purpose. To test two in vitro human nasal epithelial cell culture systems f
or their ability to screen the effects of pharmaceutical compounds on cilia
ry beating.
Methods. Human nasal epithelial cells were cultured as monolayer and in a s
equential monolayer-suspension culture with in vitro ciliogenesis. The infl
uence of reference cilio-stimulatory compounds (glycocholate, isoprenaline)
, reference cilio-inhibitory compounds (chlorocresol, diphenhydramine) and
pH on ciliary beating was investigated using computerized microscope photom
etry.
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 irreve
rsibly increased CBF of the cells by 14 +/- 3% (monolayer) and 17 +/- 4% (s
uspension). Chlorocresol (0.005% w/ V) reversibly reduced the CBF of the ce
lls by 50 +/- 6% (monolayer) and 34 +/- 4% (suspension); at a higher concen
tration (0.1% w/v) it resulted in instantaneous and irreversible ciliostasi
s. Diphenhydramine (0.1% w/v) reversibly reduced CBF in both culture system
s by 45 +/- 13% (monolayer) and 69 +/- 5% (suspension); irreversible cilio-
stasis occurred in less than 2 minutes in both culture systems upon cell ex
posure 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 beati
ng 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 effec
ts of pharmaceutical compounds on ciliary beating. Especially the sequentia
l monolayer-suspension culture appears to be very promising as ciliary acti
vity can be preserved for as long as 6 months.