The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity.
The Duffy antigen receptor for chemokines transports chemokines and supports their promigratory activity.
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Duffy抗原趋化因子受体(DARC)属于沉默的七螺旋趋化因子受体家族，不与G蛋白偶联，不能传递可测量的细胞内信号。DARC结合了大多数炎性趋化因子，并在静脉内皮细胞上显著表达，其功能一直存在争议。在这里，我们显示DARC，像其他沉默的受体一样，内化趋化因子，但不能有效地清除它们。相反，DARC介导的趋化因子跨细胞作用，导致完整趋化因子的顶端保留和更多的白细胞在表达DARC的单层之间迁移。血管内皮细胞上过表达DARC的小鼠可增强趋化因子诱导的白细胞外渗和接触性超敏反应。因此，趋化因子与DARC的相互作用支持它们在体外和体内对相对白细胞的活性。
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.