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Characterisation of guinea pig precision-cut lung slices: comparison with human tissues

¹ Research Center Borstel, Borstel, and, ³ Institute of Pharmacology and Toxicology, RWTH Aachen, Aachen, Germany. ² Unit for Experimental Asthma and Allergy Research, Division of Physiology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

CORRESPONDENCE: C. Martin, Division Pulmonary Pharmacology, Research Center Borstel, Leibniz Center for Medicine and Biosciences, Parkallee 22, D-23845 Borstel, Germany. Fax: 49 4537188778. E-mail: cmartin{at}fz-borstel.de

Keywords: Airway smooth muscle, eicosanoids, live dead staining, lung explants, ovalbumin, 2-photon microscopy

Received: January 12, 2006
Accepted May 22, 2006

Precision-cut lung slices (PCLS) allow comparison of the airway responses of different species under identical experimental conditions. The aim of this study was to establish and characterise PCLS from guinea pigs (GPs) and to compare them with human PCLS.

GP 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, expressed as nM) for agonist-induced bronchoconstriction in GP and human PCLS, respectively, were: leukotriene D₄ (1.8, 5.0); thromboxane (16, 1.3); serotonin (69, unresponsive); histamine (217, 2,170); and methacholine (231, 234). Allergen-induced bronchoconstriction of passively sensitised PCLS was attenuated by histamine or thromboxane-prostanoid receptor antagonists and was almost completely prevented by their combination with leukotriene receptor antagonists. Airways pre-contracted with methacholine were relaxed by the ß-agonist salbutamol or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Simultaneous studies of airways and vessels are possible with, for example, 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, these data show that guinea pig lungs are a more appropriate model for human airway pharmacology than lungs from rats or mice.

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