Role of plasma kallikrein-kinin system activation in synovial recruitment of endothelial progenitor cells in experimental arthritis.
Role of plasma kallikrein-kinin system activation in synovial recruitment of endothelial progenitor cells in experimental arthritis.
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DOI：
10.1002/art.34607
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发表时间：
2012-11
影响因子：
--
通讯作者：
Wu, Yi
中科院分区：
文献类型：
--
作者：
Dai, Jihong;Agelan, Alexis;Yang, Aizhen;Zuluaga, Viviana;Sexton, Daniel;Colman, Robert W.;Wu, Yi
目的：探讨血浆激肽释放酶-激肽系统（KKS）的激活是否介导了关节炎滑膜组织内皮祖细胞（EPCs）的募集。从刘易斯大鼠骨髓中分离EPCs，并通过祖细胞谱系标志物的表达和功能特性对其进行表征。将EPCs静脉注射到患关节炎的刘易斯大鼠体内，观察其在炎症滑膜中的募集和新生血管的形成。使用血浆激肽释放酶抑制剂EPI-KAL 2和抗激肽释放酶抗体13 G11检查血浆KKS的作用。用透射电镜观察缓激肽及其受体在内皮细胞动员中的作用。刘易斯大鼠EPCs具有较强的管腔和空泡形成能力，表达缓激肽2型受体（B2 R）和祖细胞标志物CD 34和Sca-1。在患有关节炎的刘易斯大鼠中，EPCs在急性期被募集到发炎的滑膜中并形成新生血管。通过EPI-KAL 2和13 G11抑制血浆激肽释放酶显著抑制了EPC的滑膜募集和滑膜细胞的过度增殖。缓激肽浓度依赖性地刺激EPCs的TEM，这是由B2 R介导的，因为通过沉默RNA来敲低B2 R完全阻断缓激肽刺激的TEM。此外，缓激肽选择性上调归巢受体C-X-C趋化因子受体4型（CXCR-4）在EPCs的表达。这些观察结果表明，血浆KKS激活在关节炎中的EPCs的滑膜募集中的新作用，通过激肽释放酶激活和B2 R依赖性机制起作用。B2 R可能通过上调CXCR-4参与EPCs的动员。
To examine whether the activation of plasma kallikrein-kinin system (KKS) mediates synovial recruitment of endothelial progenitor cells (EPCs) in arthritis. EPCs were isolated from Lewis rat bone marrow and characterized by the expression of progenitor cell lineage markers and functional property. EPCs were intravenously injected into Lewis rats bearing arthritis, their recruitment and formation of de novo blood vessels in inflamed synovium were evaluated. The role of plasma KKS was examined using a plasma kallikrein inhibitor EPI-KAL2 and an anti-kallikrein antibody 13G11. Transendothelial migration (TEM) assay was used to determine the role of bradykinin and its receptor in EPC mobilization. Lewis rat EPCs exhibited strong capacities to form tubes and vacuoles, and expressed higher level of bradykinin type 2 receptor (B2R) and progenitor cell markers CD34 and Sca-1. In Lewis rats bearing arthritis, EPCs were recruited into inflamed synovium at acute phase and formed de novo blood vessels. Inhibition of plasma kallikrein by EPI-KAL2 and 13G11 significantly suppressed synovial recruitment of EPCs and hyperproliferation of synovial cells. Bradykinin concentration-dependently stimulated TEM of EPCs, which was mediated by B2R, as the knockdown of B2R by silencing RNA completely blocked bradykinin-stimulated TEM. Moreover, bradykinin selectively upregulated the expression of homing receptor C-X-C chemokine receptor type 4 (CXCR-4) in EPCs. These observations demonstrate a novel role for plasma KKS activation in the synovial recruitment of EPCs in arthritis, acting via kallirein activation and B2R-dependent mechanisms. B2R might be involved in the mobilization of EPCs via upregulation of CXCR-4.
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影响因子：
4.2
作者：
Szekanecz, Zoltan;Besenyei, Timea;Paragh, Gyoergy;Koch, Alisa E.
通讯作者：
Koch, Alisa E.
影响因子：
4
作者：
Wu, Y;Singh, S;Birge, RB
通讯作者：
Birge, RB
DOI：
10.1016/s0162-3109(97)00023-4
发表时间：
1997-06-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Bond, AP;Lemon, M;Bhoola, KD
通讯作者：
Bhoola, KD
影响因子：
4.8
作者：
DELACADENA, RA;STADNICKI, A;COLMAN, RW
通讯作者：
COLMAN, RW
影响因子：
37.8
作者：
Grisar, J;Aletaha, D;Smolen, JS
通讯作者：
Smolen, JS