PMID- 28399855
OWN - NLM
STAT- MEDLINE
DCOM- 20171130
LR  - 20231112
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Apr 11
TI  - Characterisation of a murine model of the late asthmatic response.
PG  - 55
LID - 10.1186/s12931-017-0541-x [doi]
LID - 55
AB  - BACKGROUND: The incidence of asthma is increasing at an alarming rate. While the 
      current available therapies are effective, there are associated side effects and 
      they fail to adequately control symptoms in all patient subsets. In the search to 
      understand disease pathogenesis and find effective therapies hypotheses are often 
      tested in animal models before progressing into clinical studies. However, 
      current dogma is that animal model data is often not predictive of clinical 
      outcome. One possible reason for this is the end points measured such as 
      antigen-challenge induced late asthmatic response (LAR) is often used in early 
      clinical development, but seldom in animal model systems. As the mouse is 
      typically selected as preferred species for pre-clinical models, we wanted to 
      characterise and probe the validity of a murine model exhibiting an allergen 
      induced LAR. METHODS: C57BL/6 mice were sensitised with antigen and subsequently 
      topically challenged with the same antigen. The role of Alum(TM) adjuvant, 
      glucocorticoid, long acting muscarinic receptor antagonist (LAMA), TRPA1, CD4(+) 
      and CD8(+) T cells, B cells, Mast cells and IgE were determined in the LAR using 
      genetically modified mice and a range of pharmacological tools. RESULTS: Our data 
      showed that unlike other features of asthma (e.g. cellular inflammation, elevated 
      IgE levels and airway hyper-reactivity (AHR) the LAR required Alum(TM)adjuvant. 
      Furthermore, the LAR appeared to be sensitive to glucocorticoid and required 
      CD4(+) T cells. Unlike in other species studied, the LAR was not sensitive to 
      LAMA treatment nor required the TRPA1 ion channel, suggesting that airway sensory 
      nerves are not involved in the LAR in this species. Furthermore, the data 
      suggested that CD8(+) T cells and the mast cell-B-cell - IgE axis appear to be 
      protective in this murine model. CONCLUSION: Together we can conclude that this 
      model does feature steroid sensitive, CD4(+) T cell dependent, allergen induced 
      LAR. However, collectively our data questions the validity of using the murine 
      pre-clinical model of LAR in the assessment of future asthma therapies.
FAU - Baker, Katie
AU  - Baker K
AD  - Respiratory Pharmacology, Airway Disease Section, National Heart and Lung 
      Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, 
      SW7 2AZ, UK.
FAU - Raemdonck, Kristof
AU  - Raemdonck K
AD  - Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Prof. 
      Hernani Monteiro, 4200-319, Porto, Portugal.
AD  - Center for Health Technology and Services Research (CINTESIS), Faculty of 
      Medicine, University of Porto, Rua Dr. Placido da Costa, 4200-450, Porto, 
      Portugal.
FAU - Snelgrove, Robert J
AU  - Snelgrove RJ
AD  - Leukocyte Biology Section, National Heart and Lung Institute, Imperial College 
      London, London, UK.
FAU - Belvisi, Maria G
AU  - Belvisi MG
AD  - Respiratory Pharmacology, Airway Disease Section, National Heart and Lung 
      Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, 
      SW7 2AZ, UK.
AD  - Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, 
      London, UK.
FAU - Birrell, Mark A
AU  - Birrell MA
AD  - Respiratory Pharmacology, Airway Disease Section, National Heart and Lung 
      Institute, Faculty of Medicine, Imperial College London, Exhibition Road, London, 
      SW7 2AZ, UK. m.birrell@imperial.ac.uk.
AD  - Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, 
      London, UK. m.birrell@imperial.ac.uk.
LA  - eng
GR  - BB/E52708X/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - G1000758/MRC_/Medical Research Council/United Kingdom
GR  - MR/K020293/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170411
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (Antigens)
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Antigens/*immunology
MH  - Asthma/*immunology
MH  - Cytokines/*immunology
MH  - *Disease Models, Animal
MH  - Immunity, Innate/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Time Factors
PMC - PMC5387391
EDAT- 2017/04/13 06:00
MHDA- 2017/12/01 06:00
PMCR- 2017/04/11
CRDT- 2017/04/13 06:00
PHST- 2016/09/30 00:00 [received]
PHST- 2017/03/28 00:00 [accepted]
PHST- 2017/04/13 06:00 [entrez]
PHST- 2017/04/13 06:00 [pubmed]
PHST- 2017/12/01 06:00 [medline]
PHST- 2017/04/11 00:00 [pmc-release]
AID - 10.1186/s12931-017-0541-x [pii]
AID - 541 [pii]
AID - 10.1186/s12931-017-0541-x [doi]
PST - epublish
SO  - Respir Res. 2017 Apr 11;18(1):55. doi: 10.1186/s12931-017-0541-x.