title: Mast cell-driven skin inflammation is impaired in the absence of sensory nerves.
abstract: BACKGROUND
  Mast cells (MCs) and nerves can induce cutaneous inflammatory responses, both independently and by interacting with each other. However, little is known about the role of skin nerves and neuropeptides in the regulation of MC-mediated skin inflammation, and the contribution of MCs in neurogenic inflammation is still controversial.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effects of cutaneous sensory nerves on MC-driven inflammatory responses.
  
  
  METHODS
  Passive cutaneous anaphylaxis, a model for type I allergic skin responses, was studied in the presence or absence of sensory nerves by using a murine model of selective cutaneous denervation.
  
  
  RESULTS
  Passive cutaneous anaphylaxis was significantly impaired in the absence of sensory nerves. This effect was not a result of an alteration of mast cell numbers in denervated skin. Moreover, IgE-mediated activation of mast cells was markedly decreased in denervated compared with normal skin. Notably, pretreatment of mice with selective antagonists of the neuropeptides substance P and/or calcitonin gene-related peptide also resulted in decreased inflammatory responses after MC activation.
  
  
  CONCLUSIONS
  These data suggest that sensory skin nerves augment MC-driven inflammatory responses by releasing neuropeptides that increase MC degranulation.
authors.affiliation: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Siebenhaar
authors.forename: Markus
authors.initials: M
authors.lastname: Magerl
authors.forename: Eva M J
authors.initials: EM
authors.lastname: Peters
authors.forename: Sven
authors.initials: S
authors.lastname: Hendrix
authors.forename: Martin
authors.initials: M
authors.lastname: Metz
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D003714:Denervation; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D015213:Neuroimmunomodulation / Q000235:genetics; D011984:Sensory Receptor Cells / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000294:innervation* / Q000473:pathology; D013373:Substance P / Q000502:physiology
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide