In this section
@article{Baker:2017:10.1186/s12931-017-0541-x,
author = {Baker, K and Raemdonck, K and Snelgrove, RJ and Belvisi, MG and Birrell, MA},
doi = {10.1186/s12931-017-0541-x},
journal = {Respiratory Research},
title = {Characterisation of a murine model of the late asthmatic response},
url = {http://dx.doi.org/10.1186/s12931-017-0541-x},
volume = {18},
year = {2017}
}
TY - JOUR
AB - Background: The incidence of asthma is increasing at an alarming rate. While the current available therapies areeffective, there are associated side effects and they fail to adequately control symptoms in all patient subsets. In thesearch to understand disease pathogenesis and find effective therapies hypotheses are often tested in animalmodels before progressing into clinical studies. However, current dogma is that animal model data is often notpredictive of clinical outcome. One possible reason for this is the end points measured such as antigen-challengeinduced late asthmatic response (LAR) is often used in early clinical development, but seldom in animal modelsystems. As the mouse is typically selected as preferred species for pre-clinical models, we wanted to characteriseand 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 sameantigen. The role of AlumTM 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 anda range of pharmacological tools.Results: Our data showed that unlike other features of asthma (e.g. cellular inflammation, elevated IgE levels andairway hyper-reactivity (AHR) the LAR required AlumTMadjuvant. Furthermore, the LAR appeared to be sensitive toglucocorticoid and required CD4+ T cells. Unlike in other species studied, the LAR was not sensitive to LAMAtreatment nor required the TRPA1 ion channel, suggesting that airway sensory nerves are not involved in the LARin this species. Furthermore, the data suggested that CD8+ T cells and the mast cell—B-cell - IgE axis appear to beprotective 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 validit
AU - Baker,K
AU - Raemdonck,K
AU - Snelgrove,RJ
AU - Belvisi,MG
AU - Birrell,MA
DO - 10.1186/s12931-017-0541-x
PY - 2017///
SN - 1465-9921
TI - Characterisation of a murine model of the late asthmatic response
T2 - Respiratory Research
UR - http://dx.doi.org/10.1186/s12931-017-0541-x
UR - http://hdl.handle.net/10044/1/53755
VL - 18
ER -