Int Arch Allergy Immunol 2001;125(suppl 1):29–32 Regulation of Chemokine Receptor Expression in Eosinophils Hiroyuki Nagase a Misato Miyamasu b Masao Yamaguchi b Takao Fujisawa f Hiroshi Kawasaki d Ken Ohta e Kazuhiko Yamamoto b Yutaka Morita a Koichi Hirai c Departments of a Respiratory Medicine, b Allergy and Rheumatology and c Bioregulatory Function, University of Tokyo Graduate School of Medicine, d Department of Clinical Immunology and AIDS Research Center, Institute of Medical Science, University of Tokyo and e Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, and f Department of Pediatrics, National Mie Hospital, Tsu, Mie, Japan Correspondence to: Dr. Koichi Hirai Department of Bioregulatory Function, University of Tokyo Graduate School of Medicine 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655 (Japan) Tel. +81 3 3815 5411, ext. 33174, Fax +81 3 3815 5954 E-Mail hiraiko-tky@umin.ac.jp ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2001 S. Karger AG, Basel 1018–2438/01/1255–0029$17.50/0 Accessible online at: www.karger.com/journals/iaa Key Words CCR3 W CXCR4 W Eotaxin W Stromal cell-derived factor-1 W Glucocorticoid W IL-4 W IL-5 W IFN-Á Abstract Signals via chemokine receptors play an important role in the accumulation of eosinophils at allergic inflamma- tory sites. Eosinophils constitutively express CC chemo- kine receptor 3 (CCR3) and, to a lesser extent, CCR1. CCR3 is mainly responsible for migration of resting eosinophils, and its specific ligand, eotaxin, represents the most potent chemoattractant for eosinophils. Some reports also suggest the expression of CXC chemokine receptor 1 (CXCR1) and/or CXCR2 in eosinophils. In addi- tion, we recently reported the functional expression of CXCR4. The ligand of CXCR4, stromal cell-derived fac- tor-1 (SDF-1), was able to induce a strong migratory response comparable to that by eotaxin. In contrast to the CCR3/eotaxin system which is mainly regulated at the level of ligand production, the CXCR4/SDF-1 system is regulated at the level of receptor expression. CXCR4 expression was completely attenuated by IL-4 and IL-5 and upregulated by IFN-Á and dexamethasone, while CCR3 expression was only marginally affected. The bal- ance between the biological effects of these chemokine systems may affect the distribution and migration of eosinophils. Copyright © 2001 S. Karger AG, Basel Introduction A mounting body of evidence has indicated that che- mokines are essential participants in the sequence of events by which circulating eosinophils migrate and are activated under normal and disordered conditions. Based on their sequence of arranged cysteine groups, chemo- kines are categorized into four subfamilies, i.e. CXC, CC, CX3C and C chemokines. These chemokines exert a broad spectrum of biological effects on various types of leukocytes via corresponding chemokine receptors. To date, five CXC chemokine receptors (CXCRs), ten CC chemokine receptors (CCRs), one CX3C chemokine re- ceptor (CX3CR) and one X chemokine receptor (XCR) have been cloned. Eosinophils constitutively express CCR3, and, to a lesser extent, CCR1 [1, 2]. CCR3 is main- ly responsible for migration of resting eosinophils: eotax- in, a CCR3-specific ligand, represents the most potent chemoattractant as well as secretagogue for eosinophils