过敏性哮喘患者气道正五聚蛋白3（PTX3）表达：在气道平滑肌迁移和趋化因子产生中的作用
2012/07/05
摘要
背景：正五聚蛋白3（PTX3）是一个可溶性模式识别的受体，在炎症和自然免疫中具有一定的作用。PTX3由免疫细胞和结构细胞产生，然而，有关PTX3在过敏性哮喘患者气道的表达及其在过敏性哮喘中的作用了解较少。
目的和方法：研究哮喘患者气道中PTX3的表达及其在人气道平滑肌细胞（HASMC）中的功能。通过免疫组化检测轻度、中度和严重哮喘患者支气管活检样本中PTX3的表达。PTX3 mRNA和蛋白表达分别采用实时RT-PCR和ELISA检测。采用3H-胸腺嘧啶脱氧核苷整合、细胞计数和Boyden小室法分别检测细胞增殖和迁移。
结果：与健康对照相比，过敏性哮喘患者支气管组织中的PTX3免疫反应性增加，主要位于平滑肌束。HASMC结构性表达PTX3蛋白，而且TNF和IL-1β能显著上调PTX3的表达，但Th2细胞因子（IL-4、IL-9、IL-13）、Th1（IFN-γ）和Th17（IL-17）细胞因子对PTX的蛋白表达无影响。体外实验显示，与气道上皮细胞（EC）相比，基础水平和TNF刺激后，HASMC释放的PTX3显著增加。此外，PTX3能诱导CCL11/嗜酸细胞活化趋化因子-1的释放，但能抑制成纤维细胞生长因子-2（FGF-2）驱动的HASMC趋化活性。
结论：结果首次证实，哮喘患者气道PTX3表达增加。HASMC不仅能产生PTX3，而且能针对PRX3产生反应。PTX3是一个较强的、FGF-2诱导的HASMC迁移抑制因子，能上调CCL1/嗜酸细胞活化趋化因子-1的释放。PTX3有可能在过敏性哮喘中具有双重作用。
（苏楠 审校）
PLoS One. 2012;7(4):e34965. Epub 2012 Apr 18.
PLoS One. 2012;7(4):e34965. Epub 2012 Apr 18.
Source
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Abstract
BACKGROUND: Pentraxin 3 (PTX3) is a soluble pattern recognition receptor with non-redundant functions in inflammation and innate immunity. PTX3 is produced by immune and structural cells. However, very little is known about the expression of PTX3 and its role in allergic asthma.
OBJECTIVES AND METHODS: We sought to determine the PTX3 expression in asthmatic airways and its function in human airway smooth muscle cells (HASMC). In vivo PTX3 expression in bronchial biopsies of mild, moderate and severe asthmatics was analyzed by immunohistochemistry. PTX3 mRNA and protein were measured by real-time RT-PCR and ELISA, respectively. Proliferation and migration were examined using (3)H-thymidine incorporation, cell count and Boyden chamber assays.
RESULTS: PTX3 immunoreactivity was increased in bronchial tissues of allergic asthmatics compared to healthy controls, and mainly localized in the smooth muscle bundle. PTX3 protein was expressed constitutively by HASMC and was significantly up-regulated by TNF, and IL-1β but not by Th2 (IL-4, IL-9, IL-13), Th1 (IFN-γ), or Th-17 (IL-17) cytokines. In vitro, HASMC released significantly higher levels of PTX3 at the baseline and upon TNF stimulation compared to airway epithelial cells (EC). Moreover, PTX3 induced CCL11/eotaxin-1 release whilst inhibited the fibroblast growth factor-2 (FGF-2)-driven HASMC chemotactic activity.
CONCLUSIONS: Our data provide the first evidence that PTX3 expression is increased in asthmatic airways. HASMC can both produce and respond to PTX3. PTX3 is a potent inhibitor of HASMC migration induced by FGF-2 and can upregulate CCL11/eotaxin-1 release. These results raise the possibility that PTX3 may play a dual role in allergic asthma.
PLoS One. 2012;7(4):e34965. Epub 2012 Apr 18.
上一篇：
阻抑蛋白---T细胞的细胞内抗原-1（TIA-1）是Th2和Th17反应的一个关键调节子，能促进屋尘
下一篇：
俄罗斯过敏性支气管哮喘患者中Th2相关基因的多态性
