Leukotriene D4-induced mucosal damage during long observation periods in vitro.

The effect of leukotriene D4 (LTD4) on human paranasal sinus mucosa was investigated for over 1 hour up to 24 hours using a VTR system at 2,500 X in vitro. Ethmoidal sinus mucosal specimens were incubated in tissue culture, and after exposure to LTD4 the mucosal surface profile was viewed under an inverted phase-contrast microscope equipped with a VTR system on a TVscreen. LTD4-induced ultrastructural alterations, ciliostasis, alterations consisted of a coarse profile and epithelial cell exfoliation. Ciliary activity was photoelectorically measured on the screen hourly. The mucosal specimens were morphologically examined before and after exposure to LTD4 by transmission electron microscopy. LTD4 inhibited ciliary activity in a time- and dose-dependent manner at concentrations ranging from 10(-6)M to 10(-10)M, whereas LTE4 had a minimal effect on the mucosa even at the concentration of 10(-6) M. Irrigation of the mucosa with culture medium after 5-min of exposure to 10(-8) M LTD4 delayed appearance of ciliary inhibition and alteration of the mucosal surface profile, but had no effect after 15-min exposure. These effects of LTD4 on the mucosa were blocked by preincubation with the LT antagonists, FPL-55712 and Ly-171883. These results demonstrate the cytotoxic effect of LTD4 on human airway epithelium in vitro.