Tags

Type your tag names separated by a space and hit enter

Mast cell mediators cause early allergic bronchoconstriction in guinea-pigs in vivo: a model of relevance to asthma.
Clin Sci (Lond). 2013 Dec; 125(11):533-42.CS

Abstract

One feature of allergic asthma, the EAR (early allergic reaction), is not present in the commonly used mouse models. We therefore investigated the mediators involved in EAR in a guinea-pig in vivo model of allergic airway inflammation. Animals were sensitized using a single OVA (ovalbumin)/alum injection and challenged with aerosolized OVA on day 14. On day 15, airway resistance was assessed after challenge with OVA or MCh (methacholine) using the forced oscillation technique, and lung tissue was prepared for histology. The contribution of mast cell mediators was investigated using inhibitors of the main mast cell mediators [histamine (pyrilamine) and CysLTs (cysteinyl-leukotrienes) (montelukast) and prostanoids (indomethacin)]. OVA-sensitized and challenged animals demonstrated AHR (airway hyper-responsiveness) to MCh, and lung tissue eosinophilic inflammation. Antigen challenge induced a strong EAR in the sensitized animals. Treatment with a single compound, or indomethacin together with pyrilamine or montelukast, did not reduce the antigen-induced airway resistance. In contrast, dual treatment with pyrilamine together with montelukast, or triple inhibitor treatment, attenuated approximately 70% of the EAR. We conclude that, as in humans, the guinea-pig allergic inflammation model exhibits both EAR and AHR, supporting its suitability for in vivo identification of mast cell mediators that contribute to the development of asthma. Moreover, the known mast cell mediators histamine and leukotrienes were major contributors of the EAR. The data also lend further support to the concept that combination therapy with selective inhibitors of key mediators could improve asthma management.

Authors+Show Affiliations

Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23799245

Citation

Riley, Jason P., et al. "Mast Cell Mediators Cause Early Allergic Bronchoconstriction in Guinea-pigs in Vivo: a Model of Relevance to Asthma." Clinical Science (London, England : 1979), vol. 125, no. 11, 2013, pp. 533-42.
Riley JP, Fuchs B, Sjöberg L, et al. Mast cell mediators cause early allergic bronchoconstriction in guinea-pigs in vivo: a model of relevance to asthma. Clin Sci (Lond). 2013;125(11):533-42.
Riley, J. P., Fuchs, B., Sjöberg, L., Nilsson, G. P., Karlsson, L., Dahlén, S. E., Rao, N. L., & Adner, M. (2013). Mast cell mediators cause early allergic bronchoconstriction in guinea-pigs in vivo: a model of relevance to asthma. Clinical Science (London, England : 1979), 125(11), 533-42. https://doi.org/10.1042/CS20130092
Riley JP, et al. Mast Cell Mediators Cause Early Allergic Bronchoconstriction in Guinea-pigs in Vivo: a Model of Relevance to Asthma. Clin Sci (Lond). 2013;125(11):533-42. PubMed PMID: 23799245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mast cell mediators cause early allergic bronchoconstriction in guinea-pigs in vivo: a model of relevance to asthma. AU - Riley,Jason P, AU - Fuchs,Barbara, AU - Sjöberg,Lisa, AU - Nilsson,Gunnar P, AU - Karlsson,Lars, AU - Dahlén,Sven-Erik, AU - Rao,Navin L, AU - Adner,Mikael, PY - 2013/6/27/entrez PY - 2013/6/27/pubmed PY - 2013/10/18/medline SP - 533 EP - 42 JF - Clinical science (London, England : 1979) JO - Clin Sci (Lond) VL - 125 IS - 11 N2 - One feature of allergic asthma, the EAR (early allergic reaction), is not present in the commonly used mouse models. We therefore investigated the mediators involved in EAR in a guinea-pig in vivo model of allergic airway inflammation. Animals were sensitized using a single OVA (ovalbumin)/alum injection and challenged with aerosolized OVA on day 14. On day 15, airway resistance was assessed after challenge with OVA or MCh (methacholine) using the forced oscillation technique, and lung tissue was prepared for histology. The contribution of mast cell mediators was investigated using inhibitors of the main mast cell mediators [histamine (pyrilamine) and CysLTs (cysteinyl-leukotrienes) (montelukast) and prostanoids (indomethacin)]. OVA-sensitized and challenged animals demonstrated AHR (airway hyper-responsiveness) to MCh, and lung tissue eosinophilic inflammation. Antigen challenge induced a strong EAR in the sensitized animals. Treatment with a single compound, or indomethacin together with pyrilamine or montelukast, did not reduce the antigen-induced airway resistance. In contrast, dual treatment with pyrilamine together with montelukast, or triple inhibitor treatment, attenuated approximately 70% of the EAR. We conclude that, as in humans, the guinea-pig allergic inflammation model exhibits both EAR and AHR, supporting its suitability for in vivo identification of mast cell mediators that contribute to the development of asthma. Moreover, the known mast cell mediators histamine and leukotrienes were major contributors of the EAR. The data also lend further support to the concept that combination therapy with selective inhibitors of key mediators could improve asthma management. SN - 1470-8736 UR - https://www.unboundmedicine.com/medline/citation/23799245/Mast_cell_mediators_cause_early_allergic_bronchoconstriction_in_guinea_pigs_in_vivo:_a_model_of_relevance_to_asthma_ L2 - https://portlandpress.com/clinsci/article-lookup/doi/10.1042/CS20130092 DB - PRIME DP - Unbound Medicine ER -