CXCR2 mediates the recruitment of endothelial progenitor cells during allergic airways remodeling.

CXCR2 mediates the recruitment of endothelial progenitor cells during allergic airways remodeling.
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DOI:
10.1002/stem.222
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发表时间:
2009-12
期刊:
影响因子:
5.2
通讯作者:
Rankin, Sara M.
Rankin, Sara M.
中科院分区:
医学2区
文献类型:
--
作者:
Jones, Carla P.;Pitchford, Simon C.;Lloyd, Clare M.;Rankin, Sara M.

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气道重塑是哮喘的一个主要特征,包括新的支气管周围血管的形成,这被称为血管生成。在许多疾病模型中,骨髓来源的内皮祖细胞(EPC)已被证明对血管生成反应有贡献。在这项研究中,我们开始确定是否在过敏性呼吸道疾病模型中内皮祖细胞被招募到肺中,并确定在该模型中调控内皮祖细胞运输的因素。在模型的急性炎症阶段,我们观察到在第24天,支气管周围血管的数量显著增加。这种血管生成反应与可从肺中回收的内皮祖细胞数量的增加有关。培养21d后形成集落,表达CD31、von Willebrand因子和血管内皮生长因子受体2,但不表达CD45和CD14。内皮祖细胞的流入与促血管生成因子VEGF-A和CXCR2配体CXCL1和CXCL2的显著增加有关。然而,我们直接证明,虽然CXCL1和CXCL2趋化因子可以将内皮祖细胞招募到过敏原致敏小鼠的肺中,但血管内皮生长因子-A在这方面没有作用。此外,阻断CXCR2显著减少了过敏原暴露后肺内内皮祖细胞的数量,并导致过敏原攻击后支气管周围血管的数量减少,但对炎症没有影响。本文提供的数据提供了体内证据,证明CXCR2在这个过敏性呼吸道炎症模型中对EPC的募集和血管生成反应都是至关重要的。
Airway remodeling is a central feature of asthma and includes the formation of new peribronchial blood vessels, which is termed angiogenesis. In a number of disease models, bone marrow-derived endothelial progenitor cells (EPCs) have been shown to contribute to the angiogenic response. In this study we set out to determine whether EPCs were recruited into the lungs in a model of allergic airways disease and to identify the factors regulating EPC trafficking in this model. We observed a significant increase in the number of peribronchial blood vessels at day 24, during the acute inflammatory phase of the model. This angiogenic response was associated with an increase in the quantity of EPCs recoverable from the lung. These EPCs formed colonies after 21 days in culture and were shown to express CD31, von Willebrand factor, and vascular endothelial growth factor (VEGF) receptor 2, but were negative for CD45 and CD14. The influx in EPCs was associated with a significant increase in the proangiogenic factors VEGF-A and the CXCR2 ligands, CXCL1 and CXCL2. However, we show directly that, while the CXCL1 and CXCL2 chemokines can recruit EPCs into the lungs of allergen-sensitized mice, VEGF-A was ineffective in this respect. Further, the blockade of CXCR2 significantly reduced EPC numbers in the lungs after allergen exposure and led to a decrease in the numbers of peribronchial blood vessels after allergen challenge with no effect on inflammation. The data presented here provide in vivo evidence that CXCR2 is critical for both EPC recruitment and the angiogenic response in this model of allergic inflammation of the airways.
CD4+ CD25+调节T细胞体内转移后气道炎症和过度反应性的分辨率取决于白介素10。
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发表时间: 2004-03
期刊: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子: --
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