Selective suppression of Th2-mediated airway eosinophil infiltration by low-molecular weight CCR3 antagonists

• Published in: International immunology Vol. 19; no. 8; pp. 913 - 921
• Main Authors: Mori, Akio, Ogawa, Koji, Someya, Koichiro, Kunori, Yuichi, Nagakubo, Daisuke, Yoshie, Osamu, Kitamura, Fujiko, Hiroi, Takachika, Kaminuma, Osamu
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-08-2007
• Subjects: Animals; asthma; Benzamides - pharmacology; Bronchial Hyperreactivity - immunology; chemokine; Chemotaxis, Leukocyte - drug effects; Eosinophils - immunology; Eosinophils - metabolism; Inflammation - immunology; Inflammation - metabolism; Lung - drug effects; Lung - immunology; Mice; mouse; Naphthalenes - pharmacology; Neutrophils - immunology; Neutrophils - metabolism; Phenylalanine - analogs & derivatives; Phenylalanine - pharmacology; Receptors, CCR3 - antagonists & inhibitors; Receptors, CCR3 - immunology; Receptors, CCR3 - metabolism; T cell; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism; mouse; chemokine; asthma; T cell
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxm049

The effects of selective CC chemokine receptor (CCR)-3 antagonists on antigen-induced leukocyte accumulation in the lungs of mice adoptively transferred with in vitro-differentiated Th1 and Th2 were investigated. Inhalation of antigen by mice injected with Th1 and Th2 initiated the migration of T cells themselves into the lungs. Subsequently, neutrophils massively accumulated in Th1-transferred mice, whereas eosinophil infiltration was specifically induced by Th2. CCR3 antagonists, SB-297006 and/or SB-328437, suppressed antigen-induced accumulation of Th2 as well as eosinophils in the lungs, whereas they failed to affect Th1-mediated airway inflammation. Not only Th2 and eosinophil infiltration but also cellular mobilization in Th1-transferred mice was attenuated by an anti-CC chemokine ligand-11 antibody. CCR3 antagonists reduced chemokine production in the lungs of mice transferred with Th2 but not Th1, suggesting that down-regulation of chemokine synthesis is involved in the selective inhibition of Th2-mediated eosinophil infiltration by CCR3 antagonists.