Pérez-Arellano J L, Barrios M N, Martín T, Sánchez M L, Jiménez A, González-Buitrago J M
Departamento de Medicina, Universidad de Salamanca, Spain.
Respir Med. 1996 Mar;90(3):159-66. doi: 10.1016/s0954-6111(96)90158-4.
Hydrolytic enzymes [acid phosphatase, beta-glucuronidase, beta-D-N-acetyl glucosaminidase (beta-D-NAGA), lysozyme and angiotensin-converting enzyme (ACE)] are the major constituents of alveolar macrophages (AM). These enzymes play a crucial role in the pathogenesis of interstitial lung diseases. Cell-associated activity of several enzymes in alveolar macrophages obtained from control subjects (n = 5) and patients suffering five representative types of interstitial pulmonary diseases [sarcoidosis (n = 10), extrinsic allergic alveolitis (n = 5), idiopathic pulmonary fibrosis (n = 5), neoplastic infiltration of the lung (n = 5) and Pneumocystis carinii pneumonia (n = 5)] were evaluated. Cells were obtained by bronchoalveolar lavage and isolated by Ficoll-Hypaque gradient. Enzymatic activity was assessed by standardized tests. Bronchoalveolar lavage (BAL) lymphocyte counts were significantly elevated in the patients with active sarcoidosis (median: 57%), allergic extrinsic alveolitis (median: 51%) and neoplastic infiltration (median: 31%) as compared with the other groups, whereas BAL neutrophil and eosinophil counts were significantly elevated in the patients with idiopathic pulmonary fibrosis (neutrophil median: 29%; eosinophil median: 3%). The highest alveolar macrophage enzymatic activities were obtained in the active sarcoidosis group (median ACE: 23.38 microKat 10(-6) AM; median lysozyme: 8.64 nKat 10(-6) AM; median beta-glucuronidase: 324.22 U 10(-6) AM; median acid phosphatase: 0.78 nKat 10(-6) AM; median beta-D-NAGA: 1.85 nKat 10(-6) AM) which was significantly greater than in the control group (median ACE: 6.69 microKat 10(-6) AM; median lysozyme: 1.95 nKat 10(-6) AM; median beta-glucuronidase: 39.88 U 10(-6) AM; median acid phosphatase: 0.38 nKat 10(-6) AM; median beta-D-NAGA: 0.44 nKat 10(-6) AM). However, intracellular lysosomal enzymatic activities of alveolar macrophages from patients with allergic extrinsic alveolitis, a disease in which the degree of alveolar macrophage activation is maximal, were similar to those of the control group. These findings demonstrated a different pattern of expression of alveolar macrophage's hydrolytic enzymes in lymphocytic diffuse pulmonary interstitial disease. In sarcoidotic patients, hydrolytic enzymes were increased whereas in allergic extrinsic alveolitis, hydrolytic enzyme activities were similar to control groups. Indirect data suggest that the release of lysosomal enzymes by alveolar macrophages during allergic extrinsic alveolitis may be a factor involved in the pulmonary lesions appearing in this disease.
水解酶[酸性磷酸酶、β-葡萄糖醛酸酶、β-D-N-乙酰氨基葡萄糖苷酶（β-D-NAGA）、溶菌酶和血管紧张素转换酶（ACE）]是肺泡巨噬细胞（AM）的主要成分。这些酶在间质性肺疾病的发病机制中起关键作用。对来自对照组（n = 5）以及患有五种代表性间质性肺病[结节病（n = 10）、外源性过敏性肺泡炎（n = 5）、特发性肺纤维化（n = 5）、肺部肿瘤浸润（n = 5）和卡氏肺孢子虫肺炎（n = 5）]的患者的肺泡巨噬细胞中几种酶的细胞相关活性进行了评估。通过支气管肺泡灌洗获取细胞，并通过Ficoll-Hypaque梯度进行分离。通过标准化测试评估酶活性。与其他组相比，活动性结节病患者（中位数：57%）、过敏性外源性肺泡炎患者（中位数：51%）和肿瘤浸润患者（中位数：31%）的支气管肺泡灌洗（BAL）淋巴细胞计数显著升高，而特发性肺纤维化患者的BAL中性粒细胞和嗜酸性粒细胞计数显著升高（中性粒细胞中位数：29%；嗜酸性粒细胞中位数：3%）。活动性结节病组的肺泡巨噬细胞酶活性最高（ACE中位数：23.38微卡特10⁻⁶个AM；溶菌酶中位数：8.64纳卡特10⁻⁶个AM；β-葡萄糖醛酸酶中位数：324.22单位10⁻⁶个AM；酸性磷酸酶中位数：0.78纳卡特10⁻⁶个AM；β-D-NAGA中位数：1.85纳卡特10⁻⁶个AM），显著高于对照组（ACE中位数：6.69微卡特10⁻⁶个AM；溶菌酶中位数：1.95纳卡特10⁻⁶个AM；β-葡萄糖醛酸酶中位数：39.88单位10⁻⁶个AM；酸性磷酸酶中位数：0.38纳卡特10⁻⁶个AM；β-D-NAGA中位数：0.44纳卡特10⁻⁶个AM）。然而，过敏性外源性肺泡炎患者的肺泡巨噬细胞的细胞内溶酶体酶活性与对照组相似，过敏性外源性肺泡炎是一种肺泡巨噬细胞激活程度最大的疾病。这些发现表明淋巴细胞性弥漫性肺间质疾病中肺泡巨噬细胞水解酶的表达模式不同。在结节病患者中，水解酶增加，而在过敏性外源性肺泡炎中，水解酶活性与对照组相似。间接数据表明，过敏性外源性肺泡炎期间肺泡巨噬细胞释放溶酶体酶可能是该疾病中出现肺部病变的一个因素。
