Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
Respir Res. 2010 Oct 4;11(1):134. doi: 10.1186/1465-9921-11-134.
Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammatory cells upon stimuli such as interleukin-1β (IL-1β), we hypothesized that PTX3 is involved in COPD pathogenesis.
We evaluated whether cigarette smoke (CS) triggers pulmonary and systemic PTX3 expression in vivo in a murine model of COPD. Using immunohistochemical (IHC) staining, we observed PTX3 expression in endothelial cells of lung venules and veins but not in lung arteries, airways and parenchyma. Moreover, ELISA on lung homogenates and semi-quantitative scoring of IHC-stained sections revealed a significant upregulation of PTX3 upon subacute and chronic CS exposure. Interestingly, PTX3 expression was not enhanced upon subacute CS exposure in IL-1RI KO mice, suggesting that the IL-1 pathway is implicated in CS-induced expression of vascular PTX3. Serum PTX3 levels increased rapidly but transiently after acute CS exposure.To elucidate the functional role of PTX3 in CS-induced responses, we examined pulmonary inflammation, protease/antiprotease balance, emphysema and body weight changes in WT and Ptx3 KO mice. CS-induced pulmonary inflammation, peribronchial lymphoid aggregates, increase in MMP-12/TIMP-1 mRNA ratio, emphysema and failure to gain weight were not significantly different in Ptx3 KO mice compared to WT mice. In addition, Ptx3 deficiency did not affect the CS-induced alterations in the pulmonary (mRNA and protein) expression of VEGF-A and FGF-2, which are crucial regulators of angiogenesis.
CS increases pulmonary PTX3 expression in an IL-1 dependent manner. However, our results suggest that either PTX3 is not critical in CS-induced pulmonary inflammation, emphysema and body weight changes, or that its role can be fulfilled by other mediators with overlapping activities.
慢性阻塞性肺疾病（COPD）与气道、肺实质和肺血管的异常炎症反应和结构改变有关。由于 Pentraxin-3（PTX3）是炎症反应的调节剂，并且在白细胞介素-1β（IL-1β）等刺激物作用下由内皮细胞和炎症细胞产生，我们假设 PTX3 参与 COPD 的发病机制。
我们评估了香烟烟雾（CS）是否在 COPD 的小鼠模型中体内触发肺和全身 PTX3 的表达。通过免疫组织化学（IHC）染色，我们观察到 PTX3 在肺小静脉和静脉的内皮细胞中表达，但不在肺动脉、气道和实质中表达。此外，对肺匀浆进行 ELISA 检测和对 IHC 染色切片进行半定量评分显示，亚急性和慢性 CS 暴露后 PTX3 表达显著上调。有趣的是，在亚急性 CS 暴露的 IL-1RI KO 小鼠中，PTX3 表达没有增强，表明 IL-1 途径参与 CS 诱导的血管 PTX3 表达。血清 PTX3 水平在急性 CS 暴露后迅速但短暂升高。为了阐明 PTX3 在 CS 诱导的反应中的功能作用，我们在 WT 和 Ptx3 KO 小鼠中检查了 CS 诱导的肺部炎症、蛋白酶/抗蛋白酶平衡、肺气肿和体重变化。与 WT 小鼠相比，CS 诱导的肺部炎症、支气管周围淋巴样聚集、MMP-12/TIMP-1 mRNA 比值增加、肺气肿和体重减轻在 Ptx3 KO 小鼠中没有显著差异。此外，Ptx3 缺乏不影响 CS 诱导的血管内皮生长因子-A（VEGF-A）和成纤维细胞生长因子-2（FGF-2）在肺中的（mRNA 和蛋白）表达改变，这两者是血管生成的关键调节剂。
CS 以依赖于 IL-1 的方式增加肺 PTX3 的表达。然而，我们的结果表明，PTX3 要么在 CS 诱导的肺部炎症、肺气肿和体重变化中不是关键因素，要么其作用可以被具有重叠活性的其他介质所取代。
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