Characterization of guinea pig precision-cut lung slices: Comparison with human tissues

Precision-cut lung slices (PCLS) allow comparison of airway responses of different species under identical experimental conditions. Our aim was to establish and characterize PCLS from guinea pigs (GP) and to compare them to human PCLS. Guinea pig PCLS were prepared according to previously published procedures with the exception that the agarose solution and the initial incubation medium contained isoproterenol to avoid post mortem airway contraction. The median effective concentrations (EC50 [nM]) for agonist-induced bronchoconstriction in GP and human PCLS were: leukotriene D4 (1.8, 5.0), thromboxane (16, 1.3), serotonin (69, unresponsive), histamine (217, 2170), and methacholine (231, 234). Allergen-induced bronchoconstriction of passively sensitized PCLS was attenuated by histamine or thromboxane-prostanoid (TP)-receptor antagonists and was almost completely prevented by their combination with leukotriene receptor antagonists. Airways precontracted with methacholine were relaxed by the β-agonist salbutamol or the phosphodiesterase (PDE)inhibitor IBMX. Studies of both airways and vessels are applicable with EC50 values for endothelin-1 of 37 nM (pulmonary arteries), 10 nM (pulmonary veins), and 9.6 nM (airway). When compared with previous findings in rat and mouse, our data show that GP lungs are a more appropriate model for human airway pharmacology than are lungs from rats or mice.