Mechanism of NK1-mediated bronchoconstriction in passively sensitized human lung tissue.

Increasing evidences point to a functional unit from mast cell and sensory nerve as a key component of pathophysiological responses. Here we propose a subpopulation of neurokinin-1 receptor (NK1R) expressing mast cells in the peripheral tissue of humans to be involved in airway hyperresponsivness (AHR). Human precision cut lung slices PCLS were generated using resection material from lung tumor patients andpassivly sensitized with plasma from HDM-allergic patients. Tissue was treated with 10 µM histamine 1 receptor (H1R) or 100µM NK1R antagonists or a monoclonal antibody against IgE (mab IgE) during sensitization. Subsequently, bronchoconstriction was provoked with the sensory nerve agonist capsaicin. Bronchoconstriction was measured by videomicroscopy. The reduction of the airway area in percentage of initial airway area was analysed. Mast cell tryptase, IgE and NK1R immunostaining was performed in PCLS in order to visualize mast cell subpopulations. Immunostaining of sensory nerve fibers and mast cells showed anatomical proximity in the airways. A subpopulation of NK1 receptor positive mast cells were identified. After passive sensitization, capsaicin‑induced bronchoconstriction showed reduction of the airway area of 40%. Capsaicin‑induced bronchoconstriction was completely inhibited by pre-incubation with NK1R and H1R antagonists or mab IgE. Capsaicin-induced significant increase in bronchoconstriction in passive sensitized human PCLS. Capsaicin induced bronchoconstriction under asthmatic conditions is mediated by a process involving a subpopulation of NK1R positive mast cells.