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J. Biol. Chem., Vol. 279, Issue 26, 26807-26810, June 25, 2004

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Chemokines Generally Exhibit Scavenger Receptor Activity through Their Receptor-binding Domain^*

Takeshi Shimaoka, Takashi Nakayama, Kunio Hieshima, Noriaki Kume¶, Noriko Fukumoto, Manabu Minami¶, Kazutaka Hayashida¶, Toru Kita¶, Osamu Yoshie, and Shin Yonehara||

From the Graduate School of Biostudies and Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan, the Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama 589-8511, Japan, and the ^¶Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan

Chemokines are a family of cytokines that induce directed migration of various types of leukocytes through specific interactions with a group of seven transmembrane receptors. Scavenger receptors are a heterogenous family of transmembrane molecules that commonly bind and uptake oxidized low density lipoprotein and bacteria. Here, we show that not only CXC chemokine 16 (CXCL16)/SR-PSOX, a transmembrane chemokine with scavenger receptor activity, but also 12 out of 15 chemokines examined efficiently bound scavenger receptor ligands in competition with cells expressing their specific chemokine receptors. Furthermore both the chemotactic and scavenger receptor activities of SR-PSOX/CXCL16 were similarly impaired in a series of mutants altered in the chemokine domain, indicating that SR-PSOX/CXCL16 binds scavenger receptor ligands as well as CXCR6 using highly overlapping binding motifs. Taken together, chemokines generally have scavenger receptor-like activity through their receptor-binding domain, suggesting a close evolutionary relationship between chemokines and scavenger receptors.

Received for publication, April 13, 2004

^* This work was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan and from Solution Oriented Research for Science and Technology of Japan Science and Technology Corporation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Graduate School of Biostudies and Inst. for Virus Research, Kyoto University, Shogoin Kawahara-cho 53, Sakyo-ku, Kyoto 606-8507, Japan. Tel.: 81-75-751-4783; Fax: 81-75-751-4784; E-mail: syonehar{at}virus.kyoto-u.ac.jp.

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