Pneumologie 2011; 65 - A64
DOI: 10.1055/s-0031-1296155

Airway dendritic cell behaviour is influenced by neuropeptide release from sensory nerves

S Voedisch 1, S Rochlitzer 1, E Spies 1, A Braun 1
  • 1Department of Airway Immunology, Fraunhofer ITEM, Hannover

The airway mucosal epithelium permanently faces airborne particles. A network of immune cells patrols at this frontier to the environmental surface. The interplay of immune cells is orchestrated by different mediators. In the current study we questioned whether neuropeptides can alter key features of DC as there are movement behavior and phagocytosis capacity. With a two-photon microscopic time-lapse analysis of DC in the airways of ex vivo vital lung sections of CD11c-EYFP transgenic mice we focused on the influence of neuropeptides on dendritic cells (DC). Additionally, with a confocal microscopic approach and by means of particles being fluorescent in the phagolysosomal milieu we determined the phagocytosis capacity of CD11c+ cells. Irritation, here mimicked by electrical field stimulation (EFS) leads to an unspecific release of several neuropeptides from nerves. After EFS of vital lung slices, airway DC showed an increased motility. In subsequent experiments this effect could be reproduced by specific application of the neuropeptide calcitonin gene-related peptide (CGRP). In contrast, the application of the neuropeptide vasoactive intestinal peptide (VIP) led to a decrease of airway DC motility. Furthermore, the EFS-mediated effect could specifically be blocked by pre-treatment with the neuropeptide receptor antagonist CGRP8–37. Additionally, neuropeptides CGRP, VIP and Substance P (SP) negatively affected the phagocytosis capacity of bone marrow-derived and whole lung CD11c+ cells. We then cross-linked these data with the in vivo situation by analysing DC motility in two different asthma models. Both in the acute and prolonged asthma model we could determine altered neuropeptide content in the airways combined with a differenzial DC motility. In summary, these data suggest that neuropeptides alter key features motility and phagocytosis of mouse airway DC. Furthermore we presume that neuropeptides are responsible for fine-tuning of DC behaviour in the airways upon external stimuli. This work was funded by SFB587.