A model of neuronal hyperreactivity in passive sensitized human organotypic tissue

Obstructive lung diseases are characterized by increased sensitivity of the airways (AHR) including peripheral neuronal hyperreactivity. Especially TRPV 1 positive non myelinated afferent C-fibers are believed to be involved in development of AHR. Local TRPV1 positive nerves are extensively co expressed with sensory neuropeptides. Local axon reflex response leads to the release of neuropeptides and provoke neurogenic inflammation including bronchoconstriction, vasodilation, inflammatory cell migration and mast cell degranulation. Using passive sensitized organotypic human precision cut lung slices (PCLS), it is possible to reflect partly asthmatic conditions. Capsaicin induced activation of the peripheral sensory neurons in passive sensitized PCLS leads to neurogenic inflammation including bronchoconstriction and mast cell degranulation. Bronchoconstriction was analysed by videomicroscopy using cross-sectioned airways in PCLS. Mast cell degranulation was determined by histamine ELISA and confocal microscopy. In contrast to in vivo asthma models in mouse, rat or guinea pig, ex vivo human PCLS predict human situation regarding peripheral nerve and neuropeptide composition, airway constriction in response to neuropeptides, local immune cell answer and airway microanatomy. Thus passive sensitized PCLS provide a suitable model to analyse features of obstructive lung diseases, like neuronal hyperreactivity, without the use of animal experiments.