Expression of the Atypical Chemokine Receptor D6 in Human Alveolar Macrophages in COPD
Expression of the Atypical Chemokine Receptor D6 in Human Alveolar Macrophages in COPD
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DOI：
10.1378/chest.11-3220
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发表时间：
2013-01-01
期刊：
影响因子：
9.6
通讯作者：
Locati, Massimo
中科院分区：
文献类型：
--
作者：
Bazzan, Erica;Saetta, Marina;Locati, Massimo
背景：D 6是一种非典型趋化因子受体，参与小鼠急性炎症反应的降解和消退。新出现的证据表明，D 6可能在人类慢性炎症条件下表现不同。因此，我们调查的参与D 6在COPD，慢性炎症性疾病的肺部。方法：D 6表达定量免疫组化在手术切除的肺标本从16例COPD（FEV 1，57% +/- 6%预测）和18例对照组肺功能正常（9吸烟者和9非吸烟者）。结果：D 6在肺组织中主要表达于肺泡巨噬细胞（AM）中。与吸烟者和非吸烟者对照组相比，COPD患者中D 6（+）AM的百分比显著增加（两者均P <0.0005）。D 6的表达检测在转录和蛋白质水平的AM，但不是在单核细胞衍生的巨噬细胞。最后，D 6表达与免疫活化标志物（CD 8（+）T淋巴细胞、IL-32、肿瘤坏死因子-α、肿瘤坏死因子家族的B细胞活化因子、磷酸化-p38丝裂原活化蛋白激酶）呈正相关，与肺功能呈负相关结论：D 6在COPD患者AM中有表达，其表达与功能损害程度及免疫激活指标相关。AM中D 6的上调可能表明，除了其在急性炎症中的已知清除剂活性之外，D 6可能在慢性炎性病症中具有可能促进免疫活化的额外作用。胸部2013; 143（1）：98-106
Background: 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.Methods: D6 expression was quantified by immunohistochemistry in surgical resected lung specimens from 16 patients with COPD (FEV1, 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.Results: 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-alpha, B-cell activating factor of the tumor necrosis factor family, phospho-p38 mitogen-activated protein kinase) and negatively with lung function (FEV1, FEV1/FVC).Conclusions: 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. CHEST 2013; 143(1):98-106