Neuropeptides control the dynamic behavior of airway mucosal dendritic cells.
The airway mucosal epithelium is permanently exposed to airborne particles. A network of immune cells patrols at this interface to the environment. The interplay of immune cells is orchestrated by different mediators. In the current study we investigated the impact of neuronal signals on key functions of dendritic cells (DC). Using two-photon microscopic time-lapse analysis of living lung sections from CD11c-EYFP transgenic mice we studied the influence of neuropeptides on airway DC motility. Additionally, using a confocal microscopic approach, the phagocytotic capacity of CD11c(+) cells after neuropeptide stimulation was determined. Electrical field stimulation (EFS) leads to an unspecific release of neuropeptides from nerves. After EFS and treatment with the neuropeptides vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP), airway DC in living lung slices showed an altered motility. Furthermore, the EFS-mediated effect could partially be blocked by pre-treatment with the receptor antagonist CGRP(8-37). Additionally, the phagocytotic capacity of bone marrow-derived and whole lung CD11c(+) cells could be inhibited by neuropeptides CGRP, VIP, and Substance P. We then cross-linked 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 altered neuropeptide amounts and DC motility in the airways could be measured. In summary, our data suggest that neuropeptides modulate key features motility and phagocytosis of mouse airway DC. Therefore altered neuropeptide levels in airways during allergic inflammation have impact on regulation of airway immune mechanisms and therefore might contribute to the pathophysiology of asthma.
Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, Member of the German Center for Lung Research, Hannover, Germany.
Sabrina
S
Voedisch
Sabine
S
Rochlitzer
Tibor Z
TZ
Veres
Emma
E
Spies
Armin
A
Braun
D000818:Animals; D001249:Asthma / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D001980:Bronchi / Q000378:metabolism; D039521:CD11c Antigen / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology*; D006967:Hypersensitivity / Q000378:metabolism; D007107:Immune System; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008853:Microscopy / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D009092:Mucous Membrane / Q000166:cytology*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000494:pharmacology*; D010587:Phagocytosis; D013373:Substance P / Q000378:metabolism
D039521:CD11c Antigen; D009479:Neuropeptides; D013373:Substance P