The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity

被引：280

作者：

Pruenster, Monika ^{[1
]}

Mudde, Liesbeth ^{[1
]}

Bombosi, Paula ^{[1
]}

Dimitrova, Svetla ^{[1
]}

Zsak, Marion ^{[1
]}

Middleton, Jim ^{[1
,2
]}

Richmond, Ann ^{[3
,4
]}

Graham, Gerard J. ^{[5
]}

Segerer, Stephan ^{[6
,7
]}

Nibbs, Robert J. B. ^{[5
]}

Rot, Antal ^{[1
]}

机构：

[1] Novartis Inst BioMed Res, A-1230 Vienna, Austria

[2] Keele Univ, Robert Jones & Agnes Hunt Orthopaed Hosp, Sch Med, Oswestry SY10 7AG, Shrops, England

[3] Vanderbilt Univ, Sch Med, Dept Vet Affairs, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA

[5] Univ Glasgow, Glasgow Biomed Res Ctr, Div Immunol Infect & Inflammat, Glasgow G12 8TA, Lanark, Scotland

[6] Univ Munich, Med Poliklin, D-80337 Munich, Germany

[7] Univ Zurich, Clin Nephrol, CH-8091 Zurich, Switzerland

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 01期

关键词：

BLOOD-GROUP ANTIGEN; IN-VIVO; ENDOTHELIAL-CELLS; HEPARAN-SULFATE; RHEUMATOID-ARTHRITIS; NEGATIVE INDIVIDUALS; UP-REGULATION; BONE-MARROW; DARC; D6;

D O I：

10.1038/ni.1675

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

The Duffy antigen receptor for chemokines (DARC) belongs to a family of 'silent' heptahelical chemokine receptors that do not couple to G proteins and fail to transmit measurable intracellular signals. DARC binds most inflammatory chemokines and is prominently expressed on venular endothelial cells, where its function has remained contentious. Here we show that DARC, like other silent receptors, internalized chemokines but did not effectively scavenge them. Instead, DARC mediated chemokine transcytosis, which led to apical retention of intact chemokines and more leukocyte migration across monolayers expressing DARC. Mice overexpressing DARC on blood vessel endothelium had enhanced chemokine-induced leukocyte extravasation and contact-hypersensitivity reactions. Thus, interactions of chemokines with DARC support their activity on apposing leukocytes in vitro and in vivo.

引用

页码：101 / 108

页数：8

共 53 条

[1]

Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression [J].