Selective suppression of Th2-mediated airway eosinophil infiltration by low-molecular weight CCR3 antagonists.
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.
Mori
Akio
A
Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, 18-1 Sakuradai, Sagamihara, Kanagawa 228-8522, Japan. mori-kkr@umin.ac.jp
Ogawa
Koji
K
Someya
Koichiro
K
Kunori
Yuichi
Y
Nagakubo
Daisuke
D
Yoshie
Osamu
O
Kitamura
Fujiko
F
Hiroi
Takachika
T
Kaminuma
Osamu
O
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009281:Naphthalenes / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism