Effects of the cysteinyl leukotriene receptor antagonist, montelukast, on eosinophil differentiation in an experimental mouse model of allergic rhinitis

Crawford, L., Saito, H., Inman, M. D. and Denburg, J. A. (2002) Effects of the cysteinyl leukotriene receptor antagonist, montelukast, on eosinophil differentiation in an experimental mouse model of allergic rhinitis. Journal of Allergy and Clinical Immunology, 109(1), S296-S296. (doi:10.1016/S0091-6749(02)82041-3)

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Publisher's URL: http://dx.doi.org/10.1016/S0091-6749(02)82041-3

Abstract

The cysteinyl leukotriene (CysLT) LTD 4 is a potent lipid mediator which is synthesized and released from various inflammatory cells, and contributes to the pathophysiology associated with allergic disease. The cloning and characterization of the LTD 4 receptor (CysLTtR), has provided a useful target for therapy of rhinitis and asthma; in particular, montelukast sodium is a selective antagonist that binds with high affinity to CysLT]R on the surface of eosinophils and their progenitors. In the current study, we investigated the effects of montelukast on bone marrow eosinophil progenitor responses, using our recently developed experimental murine model of allergic rhinitis. BALB/c mice were sensitized and challenged with ovalbumin (OVA), and montelukast (5 mg/kg) or placebo was administered by gavage, for 1 or 2 wk, 1 hr before daily intra-nasal OVA challenge. Bone marrow colony assays in methylcellulose were performed, and day 6 eosinophil/basophil colony forming units (Eo/Baso-CFU) were enumerated. Colony cells (day 10) were isolated and histologically stained to allow morphologic assessment of eosinophil differentiation. Bone marrow Eo/Baso-CFU numbers, grown in the presence of interleukin 5 (IL-5) in vitro, were significantly lower than that those from controls in 2 wk (p<0.002), but not 1 wk, montelukast-treated mice. Highly significant suppression of eosinophil maturation compared to control (p<0.001) was observed in colony cells from both 1 wk and 2 wk montelukast-treated groups. These results indicate that montelukast, presumably via CysLT] R antagonism, limits the number of progenitors that differentiate into mature eosinophils; the combination of reduced CFU, as well as lower numbers of mature eosinophils per CFU, suggests that these effects may be occurring at more than one stage of eosinophil differentiation. The anti-allergic effects of montelukast may include targeting the recruitment of eosinophil progenitors from the bone marrow.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stewart, Ms Lynn
Authors: Crawford, L., Saito, H., Inman, M. D., and Denburg, J. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Allergy and Clinical Immunology
Journal Abbr.:J. Allergy Clin. Immunol.
Publisher:Elsevier
ISSN:0091-6749
ISSN (Online):1097-6825

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