Expression, regulation, and function of atypical chemerin receptor CCRL2 on endothelial cells.
Expression, regulation, and function of atypical chemerin receptor CCRL2 on endothelial cells.
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DOI：
10.4049/jimmunol.1102871
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发表时间：
2012-07-15
期刊：
影响因子：
--
通讯作者：
Zabel BA
中科院分区：
文献类型：
--
作者：
Monnier J;Lewén S;O'Hara E;Huang K;Tu H;Butcher EC;Zabel BA
CC-趋化因子受体样2（CCRL 2）结合白细胞化学引诱物趋化蛋白，并可调节引诱物的局部水平，但其本身不支持细胞迁移。在这里，我们表明，CCRL 2和血管细胞粘附分子-1（VCAM-1）上调培养的人类和小鼠血管内皮细胞（EC）和细胞系的促炎刺激。CCRL 2的诱导依赖于NF-κB和JAK/STAT信号通路，活化的内皮细胞特异性结合chemerin。在体内，CCRL 2由肺内皮细胞以高水平组成性表达，而由肝内皮细胞以较低水平组成性表达;并且肝而不是肺EC通过受体的进一步上调而响应全身性LPS注射。总chemerin的血浆水平在CCRL 2 −/−小鼠中升高，并且与WT相比，在CCRL 2 −/−小鼠中全身性LPS治疗后显著增强。在体内急性LPS诱导的肺部炎症后，与WT相比，CCRL 2 −/−小鼠中CMKLR 1 + NK细胞向气道的募集显著受损。在体外，chemerin与内皮细胞上的CCRL 2结合，通过α4β1/VCAM-1依赖性机制触发趋化因子样受体1（CMKLR 1）阳性淋巴样细胞的牢固粘附。总之，CCRL 2由内皮细胞以组织和活化依赖性方式表达;调节循环趋化素水平及其生物活性;并增强趋化素和CMKLR 1依赖性淋巴细胞-内皮细胞体外粘附和体内炎症气道招募。它的表达和/或诱导EC的促炎刺激提供了一种新的和特定的机制，局部富集chemerin在炎症部位，调节CMKLR 1+细胞的招聘。
CC-chemokine receptor-like 2 (CCRL2) binds leukocyte chemoattractant chemerin and can regulate local levels of the attractant, but does not itself support cell migration. Here we show that CCRL2 and vascular cell adhesion molecule-1 (VCAM-1) are upregulated on cultured human and mouse vascular endothelial cells (EC) and cell lines by pro-inflammatory stimuli. CCRL2 induction is dependent on NF-κB and JAK/STAT signaling pathways, and activated endothelial cells specifically bind chemerin. In vivo, CCRL2 is constitutively expressed at high levels by lung endothelial cells and at lower levels by liver endothelium; and liver but not lung EC respond to systemic LPS injection by further upregulation of the receptor. Plasma levels of total chemerin are elevated in CCRL2−/− mice, and are significantly enhanced after systemic LPS treatment in CCRL2−/− mice compared to WT. Following acute LPS-induced pulmonary inflammation in vivo, CMKLR1+ NK cell recruitment to the airways is significantly impaired in CCRL2−/− mice compared to WT. In vitro, chemerin binding to CCRL2 on endothelial cells triggers robust adhesion of chemokine-like receptor-1 (CMKLR1)-positive lymphoid cells through an α4β1/VCAM-1-dependent mechanism. In conclusion CCRL2 is expressed by endothelial cells in a tissue and activation-dependent fashion; regulates circulating chemerin levels and its bioactivity; and enhances chemerin and CMKLR1-dependent lymphocyte-endothelial cell adhesion in vitro and recruitment to inflamed airways in vivo. Its expression and/or induction on EC by proinflammatory stimuli provide a novel and specific mechanism for the local enrichment of chemerin at inflammatory sites, regulating the recruitment of CMKLR1+ cells.
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DOI：
10.1097/nen.0b013e31816fc975
发表时间：
2008-05-01
影响因子：
3.2
作者：
Lande, Roberto;Gafa, Valerie;Coccia, Eliana Marina
通讯作者：
Coccia, Eliana Marina
DOI：
10.1084/jem.20080129
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Albanesi C;Scarponi C;Pallotta S;Daniele R;Bosisio D;Madonna S;Fortugno P;Gonzalvo-Feo S;Franssen JD;Parmentier M;De Pità O;Girolomoni G;Sozzani S
通讯作者：
Sozzani S
影响因子：
37.3
作者：
Catusse J;Leick M;Groch M;Clark DJ;Buchner MV;Zirlik K;Burger M
通讯作者：
Burger M
影响因子：
--
作者：
Galligan, CL;Matsuyama, W;Yoshimura, T
通讯作者：
Yoshimura, T
DOI：
10.1006/bbrc.1997.7981
发表时间：
1998-02-04
影响因子：
3.1
作者：
Fan, P;Kyaw, H;Li, Y
通讯作者：
Li, Y