Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova and Padova City Hospital, Padova.
Chest. 2013 Jan;143(1):98-106. doi: 10.1378/chest.11-3220.
D6 is an atypical chemokine receptor involved in chemokine degradation and resolution of acute inflammatory responses in mice. Emerging evidence suggests that D6 might behave differently in human chronic inflammatory conditions. We, therefore, investigated the involvement of D6 in the immune responses in COPD, a chronic inflammatory condition of the lung.
D6 expression was quantified by immunohistochemistry in surgical resected lung specimens from 16 patients with COPD (FEV(1), 57% ± 6% predicted) and 18 control subjects with normal lung function (nine smokers and nine nonsmokers). BAL was also obtained and analyzed by flow cytometry, immunofluorescence, and molecular analysis for further assessment of D6 involvement.
D6 expression in the lung was mainly detected in alveolar macrophages (AMs). The percentage of D6(+) AMs was markedly increased in patients with COPD as compared with both smoker and nonsmoker control subjects (P < .0005 for both). D6 expression was detected at both transcript and protein level in AMs but not in monocyte-derived macrophages. Finally, D6 expression was positively correlated with markers of immune activation (CD8(+) T lymphocytes, IL-32, tumor necrosis factor-α, B-cell activating factor of the tumor necrosis factor family, phospho-p38 mitogen-activated protein kinase) and negatively with lung function (FEV(1), FEV(1)/FVC).
D6 is expressed in AMs from patients with COPD, and its expression correlates with the degree of functional impairment and markers of immune activation. Upregulation of D6 in AMs could indicate that, besides its known scavenger activity in acute inflammation, D6 may have additional roles in chronic inflammatory conditions possibly promoting immune activation.
D6 是一种非典型趋化因子受体，参与了小鼠趋化因子的降解和急性炎症反应的消退。新出现的证据表明，D6 在人类慢性炎症情况下的行为可能不同。因此，我们研究了 D6 在 COPD 中的免疫反应中的作用，COPD 是一种肺部的慢性炎症疾病。
通过免疫组织化学方法，对 16 名 COPD 患者（FEV1，57%±6%预计值）和 18 名肺功能正常的对照者（9 名吸烟者和 9 名非吸烟者）的手术切除肺标本中的 D6 表达进行了定量。还进行了 BAL 分析，并通过流式细胞术、免疫荧光和分子分析进行了进一步评估，以评估 D6 的参与。
D6 在肺中的表达主要在肺泡巨噬细胞（AMs）中检测到。与吸烟者和非吸烟者对照组相比，COPD 患者的 D6（+）AMs 百分比明显增加（均<0.0005）。D6 在 AMs 中可检测到转录和蛋白水平，但在单核细胞衍生的巨噬细胞中则不可检测。最后，D6 表达与免疫激活标志物（CD8+T 淋巴细胞、IL-32、肿瘤坏死因子-α、肿瘤坏死因子家族的 B 细胞激活因子、磷酸化 p38 丝裂原激活蛋白激酶）呈正相关，与肺功能（FEV1、FEV1/FVC）呈负相关。
D6 在 COPD 患者的 AMs 中表达，其表达与功能损害程度和免疫激活标志物相关。D6 在 AMs 中的上调表明，除了其在急性炎症中的已知清除活性外，D6 可能在慢性炎症情况下具有额外的作用，可能促进免疫激活。
