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A Reversible, Non-invasive Method for Airway Resistance Measurements and Bronchoalveolar Lavage Fluid Sampling in Mice
Published on: April 13, 2010
Comparative study to elucidate the mechanism underlying the difference in airway hyperresponsiveness between two
Juri Fukunaga1, Masayoshi Abe, Akira Murai
1Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
International Immunopharmacology
|November 28, 2007
Summary
Genetic background influences airway hyperresponsiveness (AHR) in asthma models. Cysteinyl-leukotrienes (cysLTs) play a key role in AHR development following anaphylactic reactions.
Area of Science:
- Immunology
- Pulmonology
- Pharmacology
Background:
- Airway hyperresponsiveness (AHR) is a hallmark of asthma, but its underlying mechanisms are not fully understood.
- Different mouse strains exhibit varying degrees of AHR, suggesting a role for genetic factors.
Purpose of the Study:
- To investigate the mechanisms behind differential AHR in BALB/c and C57BL/6 mouse strains after an anaphylactic trigger.
- To elucidate the role of cysteinyl-leukotrienes (cysLTs) and their receptors in AHR.
Main Methods:
- Ovalbumin (OVA)-sensitized mice (BALB/c and C57BL/6) were challenged with OVA.
- Airway responsiveness to methacholine was measured.
- Bronchoalveolar lavage fluid (BALF) and serum IgE levels were analyzed.
- In vitro studies assessed cysLT production and receptor mRNA expression in lung tissue.
Main Results:
- BALB/c mice showed significantly higher AHR, increased eosinophils and macrophages in BALF, and elevated serum IgE compared to C57BL/6 mice post-OVA challenge.
- Pretreatment with a cysLT1 receptor antagonist (montelukast) reduced AHR and eosinophilic infiltration.
- OVA challenge induced higher cysLT production and upregulation of cysLT1R and cysLT2R mRNA in BALB/c lungs compared to C57BL/6 lungs.
Conclusions:
- The degree of AHR following an anaphylactic reaction is dependent on the genetic background of the host.
- Cysteinyl-leukotrienes and their receptors are critically involved in the development of AHR in this asthma model.
