Characterization of conventional and atypical receptors for the chemokine CCL2 on mouse leukocytes.
Characterization of conventional and atypical receptors for the chemokine CCL2 on mouse leukocytes.
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DOI：
10.4049/jimmunol.1303236
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发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Nibbs RJ
中科院分区：
文献类型：
--
作者：
Ford LB;Cerovic V;Milling SW;Graham GJ;Hansell CA;Nibbs RJ
趋化因子介导的白细胞迁移对于有效的免疫和炎症反应至关重要。常规趋化因子受体（cCKR）直接控制细胞运动，非典型趋化因子受体（ACKR）调节共表达的cCKR，并且cCKR和ACKR均内化趋化因子以限制它们在体内的丰度，这一过程被称为清除。白细胞的迁移和趋化因子清除潜力由其表达的cCKR和ACKR以及这些受体的配体特异性、信号传导特性和趋化因子内化能力决定。大多数趋化因子可以结合至少一个cCKR和一个ACKR。CCL 2可以结合CCR 2（cCKR）和两个ACKR（ACKR 1和ACKR 2）。在这里，通过使用荧光CCL 2摄取标记细胞轴承功能CCL 2受体，我们已经定义了小鼠白细胞上的CCL 2受体的表达谱，清除活性和配体特异性。我们发现，定性和定量的差异，CCR 2和ACKR 2的表达赋予个别白细胞亚群与独特的CCL 2受体概况和CCL 2清除能力。我们发现，一些细胞，包括浆细胞样树突状细胞，可以同时表达CCR 2和ACKR 2; Ly 6Chi单核细胞在体外和体内具有特别强的CCL 2清除潜力; CCR 2是一种比ACKR 2更有效的CCL 2清除剂。我们证实了CCR 2和ACKR 2的独特的、重叠的配体特异性，并且出乎意料地发现细胞环境影响CCL 7和CCL 12与CCR 2的相互作用。荧光趋化因子摄取测定是有助于提供这些新的见解CCL 2受体生物学，这些测定的灵敏度，特异性和多功能性进行了讨论。
Chemokine-directed leukocyte migration is crucial for effective immune and inflammatory responses. Conventional chemokine receptors (cCKRs) directly control cell movement, atypical chemokine receptors (ACKRs) regulate co-expressed cCKRs, and both cCKRs and ACKRs internalize chemokines to limit their abundance in vivo, a process referred to as scavenging. A leukocyte’s migratory and chemokine scavenging potential is determined by which cCKRs and ACKRs it expresses, and by the ligand specificity, signaling properties, and chemokine internalization capacity of these receptors. Most chemokines can bind at least one cCKR and one ACKR. CCL2 can bind to CCR2 (a cCKR) and two ACKRs (ACKR1 and ACKR2). Here, by using fluorescent CCL2 uptake to label cells bearing functional CCL2 receptors, we have defined the expression profile, scavenging activity, and ligand specificity of CCL2 receptors on mouse leukocytes. We show that qualitative and quantitative differences in the expression of CCR2 and ACKR2 endow individual leukocyte subsets with distinctive CCL2 receptor profiles and CCL2 scavenging capacities. We reveal that some cells, including plasmacytoid dendritic cells, can express both CCR2 and ACKR2; that Ly6Chi monocytes have particularly strong CCL2 scavenging potential in vitro and in vivo; and that CCR2 is a much more effective CCL2 scavenger than ACKR2. We confirm the unique, overlapping, ligand specificities of CCR2 and ACKR2, and, unexpectedly, find that cell context influences the interaction of CCL7 and CCL12 with CCR2. Fluorescent chemokine uptake assays were instrumental in providing these novel insights into CCL2 receptor biology, and the sensitivity, specificity and versatility of these assays is discussed.
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DOI：
10.4049/jimmunol.1000454
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Björck P;Leong HX;Engleman EG
通讯作者：
Engleman EG
DOI：
10.1152/ajplung.00061.2004
发表时间：
2005-02-01
影响因子：
4.9
作者：
Maus, UA;Wellmann, S;Lohmeyer, J
通讯作者：
Lohmeyer, J
影响因子：
6
作者：
Nibbs, RJB;Kriehuber, E;Rot, A
通讯作者：
Rot, A
影响因子：
20.3
作者：
Flaishon, L;Becker-Herman, S;Shachar, I
通讯作者：
Shachar, I
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR