Chemokines generally exhibit scavenger receptor activity through their receptor-binding domain.
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.
Shimaoka
Takeshi
T
Graduate School of Biostudies and Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Nakayama
Takashi
T
Hieshima
Kunio
K
Kume
Noriaki
N
Fukumoto
Noriko
N
Minami
Manabu
M
Hayashida
Kazutaka
K
Kita
Toru
T
Yoshie
Osamu
O
Yonehara
Shin
S
D019943:Amino Acid Substitution; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D019556:COS Cells; D002460:Cell Line; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D002522:Chlorocebus aethiops; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D018925:Chemokines; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D011994:Recombinant Proteins; C099252:oxidized low density lipoprotein