Effects of a cysteinyl leukotriene receptor antagonist on eosinophil recruitment in experimental allergic rhinitis.

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.

• Authors: Hiroko Saito, Hiroshi Morikawa, Karen Howie, Lynn Crawford, Adrian J Baatjes, Elisha Denburg, Michael M Cyr, Judah A Denburg
• Journal: Immunology (Immunology) Vol. 113 Issue 2 Pg. 246-52 (Oct 2004) ISSN: 0019-2805 [Print] England
• PMID: 15379985 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Cyclopropanes
• Interleukin-3
• Interleukin-5
• Leukotriene Antagonists
• Membrane Proteins
• Quinolines
• Receptors, Leukotriene
• Sulfides
• Granulocyte-Macrophage Colony-Stimulating Factor
• leukotriene D4 receptor
• montelukast

Topics

• Acetates (immunology)
• Animals
• Basophils (immunology)
• Bone Marrow (immunology)
• Cell Differentiation
• Culture Techniques
• Cyclopropanes
• Eosinophils (immunology)
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology)
• Hematopoiesis (immunology)
• Interleukin-3 (analysis)
• Interleukin-5 (analysis)
• Leukocyte Count
• Leukotriene Antagonists (immunology)
• Membrane Proteins (antagonists & inhibitors, immunology)
• Mice
• Mice, Inbred BALB C
• Nasal Mucosa (immunology)
• Quinolines (immunology)
• Receptors, Leukotriene (immunology)
• Rhinitis, Allergic, Perennial (immunology)
• Stem Cells (immunology)
• Sulfides