Deficiency of CXCR2, but not other chemokine receptors, attenuates autoantibody-mediated arthritis in a murine model.
Deficiency of CXCR2, but not other chemokine receptors, attenuates autoantibody-mediated arthritis in a murine model.
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DOI：
10.1002/art.27470
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发表时间：
2010-07
影响因子：
--
通讯作者：
Benoist, Christophe
中科院分区：
文献类型：
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作者：
Jacobs, Jonathan P.;Ortiz-Lopez, Adriana;Campbell, James J.;Gerard, Craig J.;Mathis, Diane;Benoist, Christophe
趋化因子在动态平衡和免疫反应中协调白细胞的运输。先前关于它们在关节炎中的作用的研究采用了具有初始适应性免疫反应和炎症效应阶段的动物模型。本研究利用K/BxN血清转移模型对关节炎效应相中的趋化因子及其受体进行了研究。进行了血清转移性关节炎的时程微阵列分析，检查了脚踝、滑液和外周血。定量RT-PCR证实趋化因子表达上调。通过将血清转移到CCR1-CCR7、CCR9、CXCR2、CXCR3、CXCR5、CX3CR1、CCL2或CCL3缺陷小鼠体内，评估趋化因子诱导的功能相关性。进一步的机制分析包括用CXCR2拮抗剂治疗关节炎小鼠，用CXCR2+/−和CXCR2−/−供体和受体进行骨髓移植，滑膜细胞的流式细胞术，以及测量CXCR2+/+和CXCR2−/−混合骨髓的小鼠关节炎关节中表达CXCR2的中性粒细胞的竞争实验。基因表达谱显示，CXCR2配体CXCL1、CXCL2和CXCL5在关节中的表达上调与疾病活动平行。与接受CXCR2抑制剂的小鼠相比，CXCR2−/−小鼠的疾病有所减轻，而其他趋化因子受体的缺乏并不影响关节炎的严重程度。CXCR2仅在造血细胞上是必需的，在滑膜中性粒细胞上广泛表达。在CXCR2缺乏的中性粒细胞存在的情况下，表达CXCR2的中性粒细胞优先被招募到关节炎关节。CXCR2(但不是其他趋化因子受体)在自身抗体介导的关节炎的发展中起关键作用，在炎症关节的中性粒细胞募集中发挥细胞自主作用。
Chemokines coordinate leukocyte trafficking in homeostasis and during immune responses. Prior studies of their role in arthritis have employed animal models with both an initial adaptive immune response and an inflammatory effector phase. This study focused on chemokines and their receptors in the effector phase of arthritis using the K/BxN serum-transfer model. A time-course microarray analysis of serum-transferred arthritis was performed, examining ankle, synovial fluid and peripheral blood. Upregulation of chemokines was confirmed by quantitative RT-PCR. The functional relevance of chemokine induction was assessed by transferring serum into mice deficient in CCR1–CCR7, CCR9, CXCR2, CXCR3, CXCR5, CX3CR1, CCL2 or CCL3. Further mechanistic analysis of CXCR2 involved treatment of arthritic mice with a CXCR2 antagonist, bone-marrow transfers with CXCR2+/− and CXCR2−/− donors and recipients, flow cytometry of synovial cells, and competition experiments measuring enrichment of CXCR2-expressing neutrophils in arthritic joints of mice with mixed CXCR2+/+ and CXCR2−/− bone-marrow. Gene-expression profiling revealed upregulation of the CXCR2 ligands CXCL1, CXCL2 and CXCL5 in the joint in parallel with disease activity. CXCR2−/− mice had attenuated disease relative to CXCR2+/− littermates, as did mice receiving the CXCR2 inhibitor, while deficiency of other chemokine receptors did not affect arthritis severity. CXCR2 was required only on hematopoietic cells and was widely expressed on synovial neutrophils. CXCR2-expressing neutrophils were preferentially recruited to arthritic joints in the presence of CXCR2-deficient neutrophils. CXCR2 (but not other chemokine receptors) is critical for the development of autoantibody-mediated arthritis, exhibiting a cell-autonomous role in neutrophil recruitment to inflamed joints.
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影响因子：
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作者：
Haringman, Jasper J.;Gerlag, Danielle M.;Tak, Paul P.
通讯作者：
Tak, Paul P.
影响因子：
37.8
作者：
Combadière, C;Potteaux, S;Mallat, Z
通讯作者：
Mallat, Z
影响因子：
4.4
作者：
Brodmerkel, CM;Huber, R;Vaddi, K
通讯作者：
Vaddi, K
影响因子：
--
作者：
Grespan, Renata;Fukada, Sandra Y.;Cunha, Fernando Q.
通讯作者：
Cunha, Fernando Q.
炎性关节炎需要中性粒细胞的白细胞B4。
DOI：
10.1084/jem.20052371
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
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作者：
通讯作者：
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