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CXCL13 在哮喘中的作用:新的治疗靶点。

Role of CXCL13 in asthma: novel therapeutic target.

机构信息

Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez, Mexico City, Mexico.

Unidad de Investigación Medica en Oncologia, CMN sXXI IMSS, Mexico City, Mexico.

出版信息

Chest. 2012 Apr;141(4):886-894. doi: 10.1378/chest.11-0633. Epub 2011 Oct 20.

Abstract

BACKGROUND

B cells play an important role in allergic asthma. However, the mechanisms by which these cells are activated in the airways remain poorly understood.

METHODS

We used a mouse model of ovalbumin (OVA)-induced allergic inflammation to study CXCL13 and to investigate the concentration of this chemokine in the BAL fluid derived from asthmatic and normal control subjects.

RESULTS

We found that OVA-challenged mice upregulate the CXCL13/CXCR5 axis, which is associated with several changes in their airways, including recruitment of B and CD4(+) cells, development of bronchial-associated lymphoid tissue, and airway inflammation. Treating sensitized mice with an anti-CXCL13 antibody reduced cell recruitment, bronchial-associated lymphoid tissue formation, and airways inflammation. Interestingly, measurements of CXCL13 using enzyme-linked immunosorbent assay showed that levels of this cytokine were significantly elevated in BAL fluid from subjects with asthma compared with control subjects (median, 162 [range, 120-296] vs 31 [range, 120-156] pg/mL; P = .005).

CONCLUSIONS

All together, these findings suggest that CXCL13 is involved in the allergic airway inflammatory process, and targeting this chemokine may constitute a novel approach in asthma.

摘要

背景

B 细胞在过敏性哮喘中发挥重要作用。然而,这些细胞在气道中被激活的机制仍知之甚少。

方法

我们使用卵清蛋白(OVA)诱导的过敏性炎症小鼠模型来研究 CXCL13,并研究哮喘和正常对照受试者的 BAL 液中这种趋化因子的浓度。

结果

我们发现,OVA 挑战的小鼠上调了 CXCL13/CXCR5 轴,这与它们气道的几个变化有关,包括 B 和 CD4+细胞的募集、支气管相关淋巴组织的发育和气道炎症。用抗 CXCL13 抗体治疗致敏小鼠可减少细胞募集、支气管相关淋巴组织形成和气道炎症。有趣的是,酶联免疫吸附试验测量的 CXCL13 表明,与对照组相比,哮喘患者的 BAL 液中这种细胞因子的水平显著升高(中位数,162[范围,120-296]与 31[范围,120-156]pg/mL;P=0.005)。

结论

综上所述,这些发现表明 CXCL13 参与了过敏性气道炎症过程,靶向这种趋化因子可能成为哮喘的一种新方法。

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