Imbalance in the expression of CXC chemokines correlates with bronchoalveolar lavage fluid angiogenic activity and procollagen levels in acute respiratory distress syndrome
Imbalance in the expression of CXC chemokines correlates with bronchoalveolar lavage fluid angiogenic activity and procollagen levels in acute respiratory distress syndrome
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DOI：
10.4049/jimmunol.169.11.6515
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发表时间：
2002-12-01
影响因子：
4.4
通讯作者：
Strieter, RM
中科院分区：
文献类型：
--
作者：
Keane, MP;Donnelly, SC;Strieter, RM
弥漫性肺泡损伤是急性呼吸窘迫综合征（ARDS）的组织病理学特征，是对多种病因的典型反应。此外，相当比例的ARDS幸存者存在残留的肺纤维化和肺功能受损。这表明最终导致ARDS慢性纤维化的弥漫性肺泡损伤的发病机制具有修复失调的特征，表现为肺泡内血管生成和纤维生成（即纤维增生和细胞外基质沉积）过度，导致进行性肺泡纤维化和肺功能受损。我们从急性呼吸窘迫综合征患者或通气对照患者中获取支气管肺泡灌洗液（BALF），并通过ELISA评估CXC趋化因子水平。我们发现，与对照组相比，ARDS患者的BALF中ELR+和ELR- CXC趋化因子的表达不平衡。通过角膜微袋测定，这种不平衡与血管生成活性相关。此外，这些水平与BALF中的前胶原I和前胶原III水平相关。相比之下，虽然血管内皮生长因子的BALF水平升高，但血管内皮生长因子似乎对血管生成活性没有显著贡献。这些发现提示CXC趋化因子通过调节血管生成在ARDS的纤维增殖期发挥重要作用。
Diffuse alveolar damage is the histopathological hallmark of acute-respiratory distress syndrome (ARDS) and is a stereotypic response to a variety of etiologies. Moreover, a significant proportion of ARDS survivors have residual pulmonary fibrosis and compromised pulmonary function. This suggests that the pathogenesis of diffuse alveolar damage that ultimately leads to the chronic fibrosis of ARDS has features of dysregulated repair exemplified by exaggerated intra-alveolar angiogenesis and fibrogenesis (i.e., fibroproliferation and deposition of extracellular matrix), leading to progressive alveolar fibrosis and impaired lung function. We obtained bronchoalveolar lavage fluid (BALF) from patients with ARDS or ventilated control patients and assessed CXC chemokine levels by ELISA. We found an imbalance in the expression of ELR+ as compared with ELR- CXC chemokines from BALF of patients with ARDS as compared with controls. This imbalance correlated with angiogenic activity as assessed by the corneal micropocket assay. Furthermore, these levels correlated with both procollagen I and procollagen III levels in BALF. In contrast, while BALF levels of vascular endothelial growth factor were elevated, vascular endothelial growth factor did not appear to be significantly contributing to the angiogenic activity. These findings suggest that CXC chemokines have an important role in the fibroproliferative phase of ARDS via the regulation of angiogenesis.