PMID- 25229890
OWN - NLM
STAT- MEDLINE
DCOM- 20151214
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - Comparison of airway responses in sheep of different age in precision-cut lung 
      slices (PCLS).
PG  - e97610
LID - 10.1371/journal.pone.0097610 [doi]
LID - e97610
AB  - 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. CONCLUSION: 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.
FAU - Lambermont, Verena A
AU  - Lambermont VA
AD  - Department of Pediatrics, Maastricht University Medical Center, Maastricht, the 
      Netherlands.
FAU - Schleputz, Marco
AU  - Schleputz M
AD  - Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, 
      Germany.
FAU - Dassow, Constanze
AU  - Dassow C
AD  - Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, 
      Germany.
FAU - Konig, Peter
AU  - Konig P
AD  - Institute of Anatomy, University of Lubeck, Airway Research Center North (ARCN), 
      Member of the German Center for Lung Research (DZL), Lubeck, Germany.
FAU - Zimmermann, Luc J
AU  - Zimmermann LJ
AD  - Department of Pediatrics, Maastricht University Medical Center, Maastricht, the 
      Netherlands.
FAU - Uhlig, Stefan
AU  - Uhlig S
AD  - Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, 
      Germany.
FAU - Kramer, Boris W
AU  - Kramer BW
AD  - Department of Pediatrics, Maastricht University Medical Center, Maastricht, the 
      Netherlands.
FAU - Martin, Christian
AU  - Martin C
AD  - Institute of Pharmacology and Toxicology, University Hospital Aachen, Aachen, 
      Germany.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20140917
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Allergens)
RN  - 0 (Biogenic Amines)
RN  - 80061L1WGD (Cimetidine)
RN  - 820484N8I3 (Histamine)
SB  - IM
MH  - Aging/*immunology
MH  - Allergens/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Biogenic Amines/pharmacology
MH  - Bronchoconstriction/drug effects
MH  - Cimetidine/pharmacology
MH  - Histamine/pharmacology
MH  - Lung/*cytology/drug effects/immunology/*physiology
MH  - *Sheep
MH  - Tissue Survival
PMC - PMC4167544
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/09/18 06:00
MHDA- 2015/12/15 06:00
PMCR- 2014/09/17
CRDT- 2014/09/18 06:00
PHST- 2013/11/22 00:00 [received]
PHST- 2014/04/22 00:00 [accepted]
PHST- 2014/09/18 06:00 [entrez]
PHST- 2014/09/18 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2014/09/17 00:00 [pmc-release]
AID - PONE-D-13-47755 [pii]
AID - 10.1371/journal.pone.0097610 [doi]
PST - epublish
SO  - PLoS One. 2014 Sep 17;9(9):e97610. doi: 10.1371/journal.pone.0097610. eCollection 
      2014.