CXCL10 can inhibit endothelial cell proliferation independently of CXCR3.
CXCL10 can inhibit endothelial cell proliferation independently of CXCR3.
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DOI：
10.1371/journal.pone.0012700
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发表时间：
2010-09-13
期刊：
影响因子：
3.7
通讯作者：
Luster AD
中科院分区：
文献类型：
--
作者：
Campanella GS;Colvin RA;Luster AD
CXCL 10（或10 kDa干扰素诱导蛋白，IP-10）是一种干扰素诱导型趋化因子，对活化的效应T细胞和表达其高亲和力G蛋白偶联受体CXCR 3的其他白细胞具有强效趋化活性。CXCL 10对其他细胞类型也有活性，包括内皮细胞和成纤维细胞。CXCL 10介导其对非白细胞作用的机制尚未完全了解。在本研究中，我们专注于CXCL 10对内皮细胞的抗增殖作用，并证明CXCL 10可以独立于CXCR 3体外抑制内皮细胞增殖。四个主要发现支持这一结论。首先，从CXCR 3缺陷型小鼠分离的原代小鼠内皮细胞与野生型内皮细胞一样有效地被CXCL 10抑制。我们还注意到，基于已发表的小鼠CXCR 3基因组序列，所提出的被认为介导CXCL 10的血管抑制活性的可变剪接形式CXCR 3-B在小鼠中不存在，因为框内终止密码子将终止小鼠中所提出的CXCR 3-B剪接变体。其次，我们通过流式细胞仪分析证明，受到CXL 10抑制的人脐静脉内皮细胞和人肺微血管内皮细胞不表达CXCR 3。第三，两种不同的中和CXCR 3抗体不抑制CXCL 10的抗增殖作用。最后，第四，利用一组CXCL 10突变体，我们表明抑制内皮细胞增殖的能力与CXCL 10的糖胺聚糖结合亲和力相关，而不是与CXCR 3结合和信号传导相关。因此，使用一个非常明确的系统，我们表明，CXCL 10可以通过CXCR 3-独立的机制抑制内皮细胞增殖。
CXCL10 (or Interferon-inducible protein of 10 kDa, IP-10) is an interferon-inducible chemokine with potent chemotactic activity on activated effector T cells and other leukocytes expressing its high affinity G protein-coupled receptor CXCR3. CXCL10 is also active on other cell types, including endothelial cells and fibroblasts. The mechanisms through which CXCL10 mediates its effects on non-leukocytes is not fully understood. In this study, we focus on the anti-proliferative effect of CXCL10 on endothelial cells, and demonstrate that CXCL10 can inhibit endothelial cell proliferation in vitro independently of CXCR3. Four main findings support this conclusion. First, primary mouse endothelial cells isolated from CXCR3-deficient mice were inhibited by CXCL10 as efficiently as wildtype endothelial cells. We also note that the proposed alternative splice form CXCR3-B, which is thought to mediate CXCL10's angiostatic activity, does not exist in mice based on published mouse CXCR3 genomic sequences as an in-frame stop codon would terminate the proposed CXCR3-B splice variant in mice. Second, we demonstrate that human umbilical vein endothelial cells and human lung microvascular endothelial cells that were inhibited by CXL10 did not express CXCR3 by FACS analysis. Third, two different neutralizing CXCR3 antibodies did not inhibit the anti-proliferative effect of CXCL10. Finally, fourth, utilizing a panel of CXCL10 mutants, we show that the ability to inhibit endothelial cell proliferation correlates with CXCL10's glycosaminoglycan binding affinity and not with its CXCR3 binding and signaling. Thus, using a very defined system, we show that CXCL10 can inhibit endothelial cell proliferation through a CXCR3-independent mechanism.
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IP-10，A -C-X-C-趋化因子，在体内引起有效的胸腺依赖性抗肿瘤反应。
影响因子：
15.3
作者：
Luster, A D;Leder, P
通讯作者：
Leder, P
DOI：
10.1084/jem.184.3.963
发表时间：
1996-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Loetscher M;Gerber B;Loetscher P;Jones SA;Piali L;Clark-Lewis I;Baggiolini M;Moser B
通讯作者：
Moser B
DOI：
10.1152/ajplung.00430.2005
发表时间：
2006-05-01
影响因子：
4.9
作者：
Aksoy, MO;Yang, Y;Kelsen, SG
通讯作者：
Kelsen, SG
影响因子：
5.4
作者：
Chang, TLY;Gordon, CJ;Trkola, A
通讯作者：
Trkola, A
DOI：
10.1084/jem.182.1.219
发表时间：
1995-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luster AD;Greenberg SM;Leder P
通讯作者：
Leder P