Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Seville, Spain.
CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Int J Chron Obstruct Pulmon Dis. 2019 Jun 20;14:1323-1332. doi: 10.2147/COPD.S188567. eCollection 2019.
Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments. Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry. A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, =0.015 and <0.001, respectively; 8-fold higher for SAA2, <0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; <0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed. The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.
先前的研究表明，动脉壁是 COPD 中炎症标志物的潜在来源。在这里，我们试图比较 COPD 患者和对照组在局部（肺血管和肺实质）和全身（外周血白细胞和血浆）部位急性反应蛋白（APR）的表达。接受择期手术疑似原发性肺癌的连续患者符合研究条件。根据肺量计检查结果，将患者分为 COPD 组或对照组。从所有参与者中获得肺血管和肺实质切片、外周血白细胞和血浆样本。通过逆转录-PCR 评估组织样本和外周血白细胞中 C 反应蛋白（CRP）和血清淀粉样蛋白 A（SAA1、SAA2 和 SAA4）的基因表达水平。通过酶联免疫吸附试验测量 CRP 和 SAA 蛋白在血浆中的水平。通过免疫组织化学评估石蜡包埋的肺组织中的蛋白质。共有 40 名 COPD 患者和 62 名对照组被纳入。我们没有发现 COPD 组和对照组之间基因表达的显著差异。CRP 和 SAA 在肺实质中的表达均高于肺血管和外周血白细胞。SAA 在肺实质中的表达明显高于肺血管（SAA1 和 SAA4 高 2 倍，=0.015 和 <0.001；SAA2 高 8 倍，<0.001）和外周血白细胞（SAA1 高 16 倍，SAA2 高 439 倍，SAA4 高 5 倍，<0.001）。未观察到炎症标志物的血浆水平与其在肺和外周血白细胞中的表达之间存在相关性。肺实质中 SAA 的表达高于肺血管和外周血白细胞。值得注意的是，APR 在肺部的表达与它们在循环血浆中的水平之间没有关联，这使得炎症蛋白从肺部漏入血液的可能性不大。基于这些结果，需要进一步研究 COPD 中其他潜在的全身性炎症来源（例如肝脏）。
