Immediate allergic response in small airways

The role of small airways in the immediate allergic response is largely unk nown. We therefore used the model of precision-cut lung slices (PCLS) in co mbination with quantitative videomicroscopy to study the early allergic res ponse to allergen in airways ranging from 50 to 900 mum. After PCLS from un treated Wistar rats had been passively sensitized for 16 h with serum from sensitized Brown Norway rats, exposure to 0.1% ovalbumin resulted in an imm ediate allergic response. Both extent (r = 0.74, p < 0.0001) and velocity ( r = 0.49, p < 0.0001) of the allergen-induced bronchoconstriction increased with decreasing airway size. In addition, we observed that smaller airways not only contracted stronger and quicker, but that they also relaxed faste r, suggesting that smaller airways are more reactive in principle. The alle rgen-induced bronchoconstriction in PCLS was prevented by the serotonin rec eptor antagonist ketanserin (IC50 6 nM), but not by antagonists directed ag ainst histamine, acetylcholine, PAF, or endothelin receptors, or by cycloox ygenase or lipoxygenase inhibitors. Like allergen, serotonin provoked respo nses that were stronger in smaller airways. These findings suggest that the immediate allergic response in rat PCLS depends largely on serotonin and t hat this response can occur in nearly all airway generations, but is most p ronounced in the smallest airways, that is, the terminal bronchioles.