Effects of a Cysteinyl Leukotriene Receptor Antagonist on Eosinophil Recruitment in Experimental Allergic Rhinitis

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2004 Sep 24

PMID 15379985

Citations 17

Authors

Hiroko Saito

Hiroshi Morikawa

Karen Howie

Lynn Crawford

Adrian J Baatjes

Elisha Denburg

Michael M Cyr

Judah A Denburg

Affiliations

Soon will be listed here.

Abstract

The cysteinyl leukotrienes (cysLTs) are potent lipid mediators in allergic disease, acting through a receptor (cysLT1-R) which can be targeted in rhinitis and asthma. We investigated the effects of cysLT1-R antagonism in experimental allergic rhinitis, focusing on bone marrow eosinophil progenitor responses. BALB/c mice were sensitized, then given daily intranasal ovalbumin for 2 weeks, with montelukast sodium (5 mg/kg or 2.5 mg/kg) or placebo by gavage. Bone marrow eosinophil/basophil colonies were enumerated, and colony cells were morphologically assessed as indices of eosinophil differentiation and maturation. Montelukast treatment resulted in a significant decrease of eosinophils in the nasal mucosa, and in either bone marrow interleukin (IL)-5-, but not IL-3-, or granulocyte-macrophage colony-stimulating factor-responsive eosinophil/basophil colony-forming units, and IL-5-stimulated eosinophil maturation. These results indicate that cysLT1-R antagonism in vivo limits both IL-5-responsive eosinophilopoiesis, acting at several stages of eosinophil differentiation and maturation. The anti-allergic effects of cysLT1-R antagonists are consistent with the concept that cysLTs and IL-5 act together in the recruitment of eosinophils and eosinophil progenitors from the marrow during upper airway allergic inflammation.

Citing Articles

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Adipose Tissue-Derived Mesenchymal Stem Cell Modulates the Immune Response of Allergic Rhinitis in a Rat Model.

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Multi-Walled Carbon Nanotubes Augment Allergic Airway Eosinophilic Inflammation by Promoting Cysteinyl Leukotriene Production.

Carvalho S, Ferrini M, Herritt L, Holian A, Jaffar Z, Roberts K Front Pharmacol. 2018; 9:585.

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Cysteinyl Leukotrienes in Eosinophil Biology: Functional Roles and Therapeutic Perspectives in Eosinophilic Disorders.

Thompson-Souza G, Gropillo I, Neves J Front Med (Lausanne). 2017; 4:106.

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Effects of leukotriene D nasal challenge on bronchial responsiveness and inflammation in asthmatic patients with allergic rhinitis.

Zhu Z, Xie Y, Guan W, Gao Y, Huang R, Xia S J Thorac Dis. 2017; 9(2):271-277.

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References

Lee E, Robertson T, Smith J, Kilfeather S . Leukotriene receptor antagonists and synthesis inhibitors reverse survival in eosinophils of asthmatic individuals. Am J Respir Crit Care Med. 2000; 161(6):1881-6. DOI: 10.1164/ajrccm.161.6.9907054. View

Sampson A . The role of eosinophils and neutrophils in inflammation. Clin Exp Allergy. 2000; 30 Suppl 1:22-7. DOI: 10.1046/j.1365-2222.2000.00092.x. View

Denburg J, Sehmi R, Saito H, Inman M, OByrne P . Systemic aspects of allergic disease: bone marrow responses. J Allergy Clin Immunol. 2000; 106(5 Suppl):S242-6. DOI: 10.1067/mai.2000.110156. View

Figueroa D, Breyer R, Defoe S, Kargman S, Daugherty B, Waldburger K . Expression of the cysteinyl leukotriene 1 receptor in normal human lung and peripheral blood leukocytes. Am J Respir Crit Care Med. 2001; 163(1):226-33. DOI: 10.1164/ajrccm.163.1.2003101. View

Bautz F, Denzlinger C, Kanz L, Mohle R . Chemotaxis and transendothelial migration of CD34(+) hematopoietic progenitor cells induced by the inflammatory mediator leukotriene D4 are mediated by the 7-transmembrane receptor CysLT1. Blood. 2001; 97(11):3433-40. DOI: 10.1182/blood.v97.11.3433. View

Cyr M, Denburg J . Systemic aspects of allergic disease: the role of the bone marrow. Curr Opin Immunol. 2001; 13(6):727-32. DOI: 10.1016/s0952-7915(01)00286-2. View

Saito H, Howie K, Wattie J, Denburg A, Ellis R, Inman M . Allergen-induced murine upper airway inflammation: local and systemic changes in murine experimental allergic rhinitis. Immunology. 2001; 104(2):226-34. PMC: 1783291. DOI: 10.1046/j.1365-2567.2001.01253.x. View

Saito H, Matsumoto K, Denburg A, Crawford L, Ellis R, Inman M . Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency. J Immunol. 2002; 168(6):3017-23. DOI: 10.4049/jimmunol.168.6.3017. View

Maekawa A, Austen K, Kanaoka Y . Targeted gene disruption reveals the role of cysteinyl leukotriene 1 receptor in the enhanced vascular permeability of mice undergoing acute inflammatory responses. J Biol Chem. 2002; 277(23):20820-4. DOI: 10.1074/jbc.M203163200. View

10.

Braccioni F, Dorman S, OByrne P, Inman M, Denburg J, Parameswaran K . The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects. J Allergy Clin Immunol. 2002; 110(1):96-101. DOI: 10.1067/mai.2002.125000. View

11.

Baatjes A, Sehmi R, Saito H, Cyr M, Dorman S, Inman M . Anti-allergic therapies: effects on eosinophil progenitors. Pharmacol Ther. 2002; 95(1):63-72. DOI: 10.1016/s0163-7258(02)00233-4. View

12.

Wu A, Chik S, Chan A, Li Z, Tsang K, Li W . Anti-inflammatory effects of high-dose montelukast in an animal model of acute asthma. Clin Exp Allergy. 2003; 33(3):359-66. DOI: 10.1046/j.1365-2222.2003.01615.x. View

13.

Dahlen S, Hedqvist P, Hammarstrom S, Samuelsson B . Leukotrienes are potent constrictors of human bronchi. Nature. 1980; 288(5790):484-6. DOI: 10.1038/288484a0. View

14.

Piper P . Formation and actions of leukotrienes. Physiol Rev. 1984; 64(2):744-61. DOI: 10.1152/physrev.1984.64.2.744. View

15.

Lewis R, Austen K, Soberman R . Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med. 1990; 323(10):645-55. DOI: 10.1056/NEJM199009063231006. View

16.

Inman M, Denburg J, Ellis R, Dahlback M, OByrne P . Allergen-induced increase in bone marrow progenitors in airway hyperresponsive dogs: regulation by a serum hemopoietic factor. Am J Respir Cell Mol Biol. 1996; 15(3):305-11. DOI: 10.1165/ajrcmb.15.3.8924277. View

17.

Boyce J, Lam B, Penrose J, Friend D, Parsons S, Owen W . Expression of LTC4 synthase during the development of eosinophils in vitro from cord blood progenitors. Blood. 1996; 88(11):4338-47. View

18.

Penrose J, Baldasaro M, Webster M, Xu K, Austen K, Lam B . Molecular cloning of the gene for mouse leukotriene-C4 synthase. Eur J Biochem. 1997; 248(3):807-13. DOI: 10.1111/j.1432-1033.1997.00807.x. View

19.

Gauvreau G, OByrne P, Moqbel R, VELAZQUEZ J, Watson R, Howie K . Enhanced expression of GM-CSF in differentiating eosinophils of atopic and atopic asthmatic subjects. Am J Respir Cell Mol Biol. 1998; 19(1):55-62. DOI: 10.1165/ajrcmb.19.1.2871. View

20.

Adachi T, Alam R . The mechanism of IL-5 signal transduction. Am J Physiol. 1998; 275(3):C623-33. DOI: 10.1152/ajpcell.1998.275.3.C623. View