Zanini Andrea, Spanevello Antonio, Baraldo Simonetta, Majori Maria, Della Patrona Sabrina, Gumiero Federico, Aiello Marina, Olivieri Dario, Saetta Marina, Chetta Alfredo
Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
Respiration. 2014;87(3):234-42. doi: 10.1159/000356749. Epub 2014 Jan 14.
Dendritic cells (DCs) have a pivotal role in the onset and regulation of innate and adaptive immune responses. Moreover, DCs can interact with angiogenic modulators, resulting in modification of their biology and participation in angiogenesis.
This study was designed to evaluate the relationship between the density of DCs, vascularity and expression of angiogenic factors [vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β and basic fibroblast growth factor (bFGF)] in the central airways of chronic obstructive pulmonary disease (COPD) patients.
The study included 20 patients with moderate/severe COPD and 8 healthy control subjects. Bronchial biopsies were evaluated by immunohistochemistry. Specimens were examined for CD83 and CD207 to mark mature and immature DCs, respectively, for collagen IV to evaluate vascularity, and for VEGF, TGF-β and bFGF.
Compared to controls, COPD patients had a significant reduction of CD83+ cells and an increased CD207/CD83 ratio (p < 0.05). Vascularity, VEGF, TGF-β and bFGF were also significantly increased in COPD patients as compared to controls (p < 0.01). In COPD patients, CD83+ cells were inversely related to VEGF and TGF-β expression (p < 0.05). Moreover, the CD207/CD83 ratio was positively related to VEGF, TGF-β and vascularity (p < 0.05). Finally, CD207+ cells were inversely related to FEV1 (p < 0.05).
Our results show a reduced maturation of DCs in COPD that was related to airway vascularity and angiogenic factors (VEGF and TGF-β). Additionally, immature DCs were significantly related to disease severity. We propose that the interplay between airway vascular changes, on one hand, and DCs maturation on the other, may play a key role in the pathogenetic mechanisms of COPD.
树突状细胞（DCs）在先天性和适应性免疫反应的启动和调节中起关键作用。此外，DCs可与血管生成调节因子相互作用，导致其生物学特性发生改变并参与血管生成。
本研究旨在评估慢性阻塞性肺疾病（COPD）患者中央气道中DCs密度、血管生成及血管生成因子[血管内皮生长因子（VEGF）、转化生长因子（TGF）-β和碱性成纤维细胞生长因子（bFGF）]表达之间的关系。
该研究纳入了20例中重度COPD患者和8名健康对照者。通过免疫组织化学对支气管活检标本进行评估。分别检测标本中用于标记成熟和未成熟DCs的CD83和CD207、用于评估血管生成的IV型胶原以及VEGF、TGF-β和bFGF。
与对照组相比，COPD患者CD83+细胞显著减少，CD207/CD83比值增加（p<0.05）。与对照组相比，COPD患者的血管生成、VEGF、TGF-β和bFGF也显著增加（p<0.01）。在COPD患者中，CD83+细胞与VEGF和TGF-β表达呈负相关（p<0.05）。此外，CD207/CD83比值与VEGF、TGF-β和血管生成呈正相关（p<0.05）。最后，CD207+细胞与第一秒用力呼气容积（FEV1）呈负相关（p<0.05）。
我们的结果显示COPD患者中DCs成熟度降低，这与气道血管生成及血管生成因子（VEGF和TGF-β）有关。此外，未成熟DCs与疾病严重程度显著相关。我们认为，一方面气道血管变化与另一方面DCs成熟之间的相互作用可能在COPD的发病机制中起关键作用。
