The Journal of Experimental Medicine
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Published online 16 January 2001.
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© The Rockefeller University Press, 0022-1007/2001/1/255/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 2, January 15, 2001 255-262


Brief Definitive Report

Prostaglandin D2 Selectively Induces Chemotaxis in T Helper Type 2 Cells, Eosinophils, and Basophils via Seven-Transmembrane Receptor CRTH2

Hiroyuki Hiraia,b, Kazuya Tanakaa, Osamu Yoshied, Kazuyuki Ogawaa, Kazumi Kenmotsua, Yasushi Takamoria, Michiko Ichimasac, Kazuo Sugamurae, Masataka Nakamuraf, Shoichi Takanoa, and Kinya Nagataa
a R&D Center, BML, Saitama 350-1101, Japan
b Graduate School of Science and Engineering, Faculty of Science, Ibaraki University, Ibaraki 310-8512, Japan
c Department of Environmental Sciences, Faculty of Science, Ibaraki University, Ibaraki 310-8512, Japan
d Department of Bacteriology, Kinki University School of Medicine, Osaka 589-8511, Japan
e Department of Microbiology and Immunology, Tohoku University School of Medicine, Miyagi 980-8575, Japan
f Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo 113-8510, Japan

Correspondence to: Kinya Nagata, R&D Center, BML, 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan. Tel:81-492-32-0440 Fax:81-492-32-5480 E-mail:nagata{at}alk.co.jp.

Prostaglandin (PG)D2, which has long been implicated in allergic diseases, is currently considered to elicit its biological actions through the DP receptor (DP). Involvement of DP in the formation of allergic asthma was recently demonstrated with DP-deficient mice. However, proinflammatory functions of PGD2 cannot be explained by DP alone. We show here that a seven-transmembrane receptor, CRTH2, which is preferentially expressed in T helper type 2 (Th2) cells, eosinophils, and basophils in humans, serves as the novel receptor for PGD2. In response to PGD2, CRTH2 induces intracellular Ca2+ mobilization and chemotaxis in Th2 cells in a G{alpha}i-dependent manner. In addition, CRTH2, but not DP, mediates PGD2-dependent cell migration of blood eosinophils and basophils. Thus, PGD2 is likely involved in multiple aspects of allergic inflammation through its dual receptor systems, DP and CRTH2.

Key Words: prostanoid receptor, G{alpha}i-type G protein, T cells, cell migration, allergic inflammation


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