Effects of a cysteinyl leukotriene receptor antagonist on eosinophil recruitment in experimental allergic rhinitis.
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.
Saito
Hiroko
H
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Morikawa
Hiroshi
H
Howie
Karen
K
Crawford
Lynn
L
Baatjes
Adrian J
AJ
Denburg
Elisha
E
Cyr
Michael M
MM
Denburg
Judah A
JA
D000085:Acetates / Q000276:immunology; D000818:Animals; D001491:Basophils / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D046508:Culture Techniques; D003521:Cyclopropanes; D004804:Eosinophils / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology; D007377:Interleukin-3 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D007958:Leukocyte Count; D020024:Leukotriene Antagonists / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D011804:Quinolines / Q000276:immunology; D018077:Receptors, Leukotriene / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D007377:Interleukin-3; D015848:Interleukin-5; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C083169:leukotriene D4 receptor; C093875:montelukast