title: Comparison of airway responses in sheep of different age in precision-cut lung slices (PCLS).
abstract: BACKGROUND
  Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS) for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages.
  
  
  METHODS
  Lambs were delivered spontaneously at term (147d) and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM) and mast cells staining were evaluated.
  
  
  RESULTS
  PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages.
  
  
  CONCLUSIONS
  PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Verena A
authors.initials: VA
authors.lastname: Lambermont
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Schlepütz
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Dassow
authors.affiliation: Institute of Anatomy, University of Lübeck, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Lübeck, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: König
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Zimmermann
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.affiliation: Department of Pediatrics, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.affiliation: Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Martin
mesh_terms: D000375:Aging / Q000276:immunology*; D000485:Allergens / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001679:Biogenic Amines / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D012756:Sheep; D014022:Tissue Survival
chemical_list: D000485:Allergens; D001679:Biogenic Amines; D002927:Cimetidine; D006632:Histamine