Am. J. Respir. Crit. Care Med., Vol 152, No. 1, Jul 1995, 81-86.
In vitro airway and tissue response to antigen in sensitized rats. Role of serotonin and leukotriene D4
T Nagase, Y Fukuchi, MJ Dallaire, JG Martin and MS Ludwig
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
We have recently demonstrated that tissue resistance increases during the
early response (ER) to antigen challenge in sensitized Brown-Norway rats.
The purpose of the present study was to investigate the in vitro airway and
tissue responses to antigen and the involvement of the potential mediators
serotonin (5-HT) and leukotriene D4 (LTD4). We sensitized Brown-Norway rats
with ovalbumin (OA) and subsequently challenged bronchial rings and
subpleural parenchymal strips with OA in the organ bath. In selected
experiments tissues were incubated with methysergide (a 5-HT receptor
antagonist), ketanserin (a 5-HT2 receptor antagonist), MK-571 (a LTD4
receptor antagonist), or MK-886 (5- lipoxygenase inhibitor) prior to
challenge. Both bronchial rings and parenchymal strips constricted in
response to OA. Methysergide and ketanserin completely inhibited OA-induced
constriction of bronchial rings. The effect of MK-571 was not significant,
whereas MK-886 partially blocked OA-induced bronchial constriction,
suggesting a potential role for LTC4 in antigen-induced airway
constriction. In parenchymal strips, methysergide, ketanserin, MK-571, and
MK-886 all partially inhibited the OA response, whereas the combinations of
methysergide and MK-571 or ketanserin and MK-886 completely ablated the
response. These data suggest that both bronchial rings and parenchymal
strips constrict after OA challenge but that the relative contributions of
5-HT and LTD4 to the allergic response in central airways and parenchymal
tissues differ.
