title: Nasal allergen deposition leads to conjunctival mast cell degranulation in allergic rhinoconjunctivitis.
abstract: BACKGROUND
  The naso-ocular interaction in allergic rhinoconjunctivitis is well recognized from epidemiological, clinical, and experimental observations. The precise mechanisms remain incompletely understood. A new mouse model of allergic rhinoconjunctivitis was used to investigate the contribution of mast cells and trigeminal ganglia activation to conjunctival (conj.) inflammation after nasal allergen provocation.
  
  
  METHODS
  Sensitized mice were exposed to ovalbumin (OVA) via the nose and/or conjunctiva, and conj. homogenates were analyzed for histamine and substance P (using ELISA) and by eosinophil peroxidase (EPO) and beta-hexosaminidase assays. The conj. effects of nasal allergen deposition were compared with those induced by the mast cell activator C48/80 and with pretreatment of the mast cell stabilizer ketotifen or the transient receptor potential channel receptor (TRP) agonist capsaicin. Protachykinin 1 (TAC1) expression was quantified in the trigeminal ganglia using real time polymerase chain reaction.
  
  
  RESULTS
  At 1 hour after nasal application of OVA, increased conj. levels of beta-hexosaminidase (0.68 ± 0.03 nm versus 0.56 ± 0.02 nm; p = 0.02), histamine (751.1 ± 52.17 ng/mL versus 546.3 ± 76.91 ng/mL; p = 0.05), and EPO (0.66 ± 0.09 nm versus 0.37 ± 0.03 nm; p = 0.02) were detected compared with saline. Higher levels of TAC1 expression were found in the trigeminal ganglia at 24 hours after OVA application (1326 ± 255 versus 687.5 ± 90.77 TAC1/beta-actin; p = 0.04). Nasal challenge with C48/80 increased substance P and beta-hexosaminidase levels in the conjunctiva, as well as TAC1 expression. Pretreatment with ketotifen resulted in lower levels of substance P as well as TAC1 expression. Destruction of sensory nerves in the nose by capsaicin reduced the OVA-induced conj. levels of substance P, histamine, and beta-hexosaminidase.
  
  
  CONCLUSIONS
  Nasal allergen deposition in sensitized mice induced trigeminal TAC1 expression and conj. mast cell degranulation. These data represent a significant step forward in understanding the close interaction between nasal and conj. inflammation in allergy.
authors.affiliation: Clinical Immunology, Department of Microbiology and Immunology, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Ina
authors.initials: I
authors.lastname: Callebaut
authors.forename: Annick
authors.initials: A
authors.lastname: De Vries
authors.forename: Brecht
authors.initials: B
authors.lastname: Steelant
authors.forename: Valérie
authors.initials: V
authors.lastname: Hox
authors.forename: Sonja
authors.initials: S
authors.lastname: Bobic
authors.forename: Laura
authors.initials: L
authors.lastname: Van Gerven
authors.forename: Jan L
authors.initials: JL
authors.lastname: Ceuppens
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hellings
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D015550:Cell Degranulation; D003233:Conjunctivitis, Allergic / Q000503:physiopathology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011498:Protein Precursors / Q000032:analysis; D065631:Rhinitis, Allergic / Q000503:physiopathology*; D013373:Substance P / Q000032:analysis; D015320:Tachykinins / Q000032:analysis; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D000485:Allergens; D011498:Protein Precursors; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D003189:p-Methoxy-N-methylphenethylamine; D001619:beta-N-Acetylhexosaminidases