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

Akio Mori, Koji Ogawa, Koichiro Someya, Yuichi Kunori, Daisuke Nagakubo, Osamu Yoshie, Fujiko Kitamura, Takachika Hiroi, Osamu Kaminuma

Index: Int. Immunol. 19(8) , 913-21, (2007)

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Abstract

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 T(h)1 and T(h)2 were investigated. Inhalation of antigen by mice injected with T(h)1 and T(h)2 initiated the migration of T cells themselves into the lungs. Subsequently, neutrophils massively accumulated in T(h)1-transferred mice, whereas eosinophil infiltration was specifically induced by T(h)2. CCR3 antagonists, SB-297006 and/or SB-328437, suppressed antigen-induced accumulation of T(h)2 as well as eosinophils in the lungs, whereas they failed to affect T(h)1-mediated airway inflammation. Not only T(h)2 and eosinophil infiltration but also cellular mobilization in T(h)1-transferred mice was attenuated by an anti-CC chemokine ligand-11 antibody. CCR3 antagonists reduced chemokine production in the lungs of mice transferred with T(h)2 but not T(h)1, suggesting that down-regulation of chemokine synthesis is involved in the selective inhibition of T(h)2-mediated eosinophil infiltration by CCR3 antagonists.