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Neuropeptides influence airway dendritic cell behavior

: Braun, Armin

American Journal of Respiratory and Critical Care Medicine 185 (2012), Abstract A2155
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2012, San Francisco/Calif.>
Fraunhofer ITEM ()

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 investigated whether neuropeptides can alter key features of dendritic cells (DC) such as 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 DC. Additionally, with a confocal microscopic approach and by means of particles becoming fluorescent in the phagolysosomal milieu we determined the phagocytosis capacity of CD11c+ cells. Neuronal irritation here mimicked by electrical field stimulation (EFS) leads to an unspecific release of several neuropeptides in 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). The EFS-mediated effect could partially be blocked by pre-treatment with the neuropeptide receptor antagonist CGRP8-37. In contrast, the application of the neuropeptide vasoactive intestinal peptide (VIP) led to a decrease of airway DC motility. Additionally, phagocytosis capacity of bone marrow-derived and whole lung CD11c+ cells could be negatively affected by neuropeptides CGRP, VIP, and Substance P. We then correlated these data with the in vivo situation by analyzing DC motility in two different OVA asthma models. Both in the acute and prolonged OVA asthma model we could determine altered neuropeptide amounts in the airways and DC motility. In summary, our data suggest that neuropeptides alter key features motility and phagocytosis of mouse airway DC and therefore might contribute to the pathophysiology of asthma.
This work was funded by the SFB 587 B4