International Immunology, Vol. 15, No. 10, pp. 1219-1227,
October 2003
© 2003 Japanese Society for Immunology
A high endothelial venule-expressing promiscuous chemokine receptor DARC can bind inflammatory, but not lymphoid, chemokines and is dispensable for lymphocyte homing under physiological conditions
1 Laboratory of Molecular and Cellular Recognition and 2 Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan 3 Laboratory of Developmental Biochemistry, Graduate School of Pharmaceutical Sciences,University of Tokyo, Tokyo 113-0033, Japan 4 Present address: Sunplanet Co., Ltd, BMR Kamiishizu Center, Gifu 503-1602, Japan
The first two authors contributed equally to this work
Correspondence to: M. Miyasaka; E-mail: mmiyasak{at}orgctl.med.osaka-u.ac.jp
Transmitting editor: K. Sugamura
Chemokines displayed on the luminal surface of blood vessels play pivotal roles in inflammatory and homeostatic leukocyte trafficking in vivo. However, the mechanisms underlying the functional regulation of chemokines on the endothelial cell surface remain ill-defined. A promiscuous chemokine receptor, the Duffy antigen receptor for chemokines (DARC), has been implicated in the regulation of chemokine functions. Here we show that DARC is selectively expressed at the mRNA and protein levels in the high endothelial venules (HEV) of unstimulated lymph nodes (LN). To examine the biological significance of DARC expression in HEV, we performed competitive binding experiments with 20 different chemokines. The results showed that DARC selectively bound distinct members of the pro-inflammatory chemokines such as CXCL1, CXCL5, CCL2, CCL5 and CCL7, but not lymphoid chemokines such as CCL21, CCL19, CXCL12 and CXCL13 that are normally expressed in HEV. CCL2 bound to DARC failed to induce a significant cytosolic [Ca2+] elevation in CCR2B-expressing cells, whereas the free form of CCL2 induced a distinct [Ca2+] elevation, suggesting that DARC down-regulates activities of pro-inflammatory chemokines upon binding. Targeted disruption of the gene encoding DARC did not induce any obvious changes in the cell number or leukocyte subsets in the peripheral and mesenteric LN. Neither did DARC deficiency significantly affect lymphocyte migration into LN. These results suggest that DARC may be a scavenger for pro-inflammatory chemokines, but not a presenting molecule for lymphoid chemokines at HEV and that it is probably functionally dispensable for lymphocyte trafficking to HEV-bearing lymphoid tissues under physiological conditions.
Keywords: chemokines, DARC, high endothelial venule, lymph node, lymphocyte homing
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Vielhauer, R. Allam, M. T. Lindenmeyer, C. D. Cohen, D. Draganovici, J. Mandelbaum, N. Eltrich, P. J. Nelson, H.-J. Anders, M. Pruenster, et al. Efficient Renal Recruitment of Macrophages and T Cells in Mice Lacking the Duffy Antigen/Receptor for Chemokines Am. J. Pathol., July 1, 2009; 175(1): 119 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Borroni, R. Bonecchi, A. Mantovani, and M. Locati Chemoattractant Receptors and Leukocyte Recruitment: More Than Cell Migration Sci. Signal., February 24, 2009; 2(59): pe10 - pe10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Zabel, S. Nakae, L. Zuniga, J.-Y. Kim, T. Ohyama, C. Alt, J. Pan, H. Suto, D. Soler, S. J. Allen, et al. Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis J. Exp. Med., September 29, 2008; 205(10): 2207 - 2220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-G. Yang, T. Tanaka, M. H. Jang, Z. Bai, H. Hayasaka, and M. Miyasaka Binding of Lymphoid Chemokines to Collagen IV That Accumulates in the Basal Lamina of High Endothelial Venules: Its Implications in Lymphocyte Trafficking J. Immunol., October 1, 2007; 179(7): 4376 - 4382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Edderkaoui, D. J. Baylink, W. G. Beamer, J. E. Wergedal, R. Porte, A. Chaudhuri, and S. Mohan Identification of mouse Duffy Antigen Receptor for Chemokines (Darc) as a BMD QTL gene Genome Res., May 1, 2007; 17(5): 577 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shen, R. Schuster, K. F. Stringer, S. E. Waltz, and A. B. Lentsch The Duffy antigen/receptor for chemokines (DARC) regulates prostate tumor growth FASEB J, January 1, 2006; 20(1): 59 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Carlsen, G. Haraldsen, P. Brandtzaeg, and E. S. Baekkevold Disparate lymphoid chemokine expression in mice and men: no evidence of CCL21 synthesis by human high endothelial venules Blood, July 15, 2005; 106(2): 444 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Puneet, S. Moochhala, and M. Bhatia Chemokines in acute respiratory distress syndrome Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L3 - L15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Prevo, S. Banerji, J. Ni, and D. G. Jackson Rapid Plasma Membrane-Endosomal Trafficking of the Lymph Node Sinus and High Endothelial Venule Scavenger Receptor/Homing Receptor Stabilin-1 (Feel-1/Clever-1) J. Biol. Chem., December 10, 2004; 279(50): 52580 - 52592. [Abstract] [Full Text] [PDF]
|
|