Formal
dehy
de (FA) exposure induces upper airways irritation and respiratory abnormalities, but its mechanisms are not un
derstood. Since mast cells are wi
dely distributed in the airways, we hypothesized that FA might modify the airways reactivity by mechanism involving their activation. Tracheal rings of rats were incubated with Dulbecco's modified medium culture containing FA (0.1 ppm) in 96-well plastic microplates in a humid atmosphere. After 30 min, 6 h, and 24–72 h, the rings were suspen
ded in an organ bath and dose–response curve to methacholine (MCh) were
determined. Incubation with FA caused a transient tracheal hyperresponsiveness to MCh that was in
depen
dent from tracheal epithelium integrity. Connective tissue mast cell
depletion caused by compound 48/80 or mast cell activation by the allergic reaction, before exposure of tracheal rings to FA prevented the increased responsiveness to MCh. LTB
4 concentrations were increased in the culture medium of tracheas incubated with FA for 48 h, whereas the LTB
4-receptor antagonist MK886 (1 μM) ad
ded before FA exposure ren
dered the tracheal rings normoreactive to MCh. In addition, FA exposure did not cause hyperresponsiveness in tracheal segments incubated with
l-arginine (1 μM).We suggest that airway connective tissue mast cells constitute the target and may provide the increased LTB4 generation as well as an elevated consumption of NO leading to tracheal hyperresponsiveness to MCh.