慢性支气管炎患者肺泡巨噬细胞及诱导痰中内皮素的研究

目的研究慢性支气管炎(慢支炎)患者诱导痰中、肺泡巨噬细胞(AM)培养上清液中及在氨茶碱和脂多糖(LPS)干预下培养上清液中内皮素(ET)的浓度变化,探讨AM源性ET在慢支炎及慢性阻塞性肺疾病(COPD)病理进展过程中的作用.方法选择慢支炎患者14例,COPD患者13例,同时选择14名健康人作为正常对照.支气管肺泡灌洗技术收集支气管肺泡灌洗液(BALF),对其细胞成分进行计数和分类;对其中26例用高渗盐水诱痰法取痰标本,放射免疫法测定诱导痰中和AM培养上清液中的ET浓度.结果(1)慢支炎组、COPD组BALF中细胞总数、中性粒细胞数、肺泡巨噬细胞数均明显高于正常对照组(P均<0.01);(2)慢支炎组和COPD组AM培养上清液中ET浓度和诱导痰中ET浓度明显高于正常对照组(P均<0.01),但慢支炎组与COPD组之间差异无显著性(P均>0.05);(3)三组的诱导痰ET浓度与AM培养上清液ET浓度呈正相关(r=0.741,P<0.01),与AM数呈正相关(r=0.597,P<0.01);(4)COPD组AM培养上清液ET浓度、诱导痰ET浓度均与一秒钟用力呼气容积占预计值%(FEV1占预计值%)呈负相关(r=-0.828,P<0.01;r=-0.748,P<0.05);(5)氨茶碱对AM培养上清液中ET浓度无影响(P>0.05),而LPS使其浓度明显升高(P<0.01).结论(1)慢支炎、COPD患者气道腔内存在非特异性气道炎症,其特点表现为中性粒细胞和巨噬细胞数目增多;(2)AM为肺内ET的重要来源之一,LPS可刺激AM分泌ET,AM源性ET可能参与了COPD阻塞性通气功能障碍的病理进展过程.

The change of concentration of endothelin derived from alveolar macrophages and in induced sputum in patients with chronic bronchitis

OBJECTIVE: To evaluate the changes of levels of endothelin (ET) in induced sputum, the culture supernatants of alveolar macrophages (AMs) and the culture supernatants of alveolar macrophages (AMs) when cultivated with aminophylline and lipopolysaccharide (LPS) in patients with chronic bronchitis and COPD. Then to investigate the role of ET derived from AMs in chronic bronchitis and COPD. METHODS: Fourteen patients with chronic bronchitis and thirteen patients with COPD were studied. Fourteen healthy were enrolled as control. Bronchoscopy and bronchial alveolar lavage were performed routinely, BAL cells were count with hemacytometer and differentater with wright stain. Sputum induction with 4% saline was performed on twenty-six subjects. The levels of ET in BALF and in the culture supernatants of AMs were measured by radioimmunoassay methods. RESULTS: (1) The number of all cells, neutrophils and AMs in BALF of patients with chronic bronchitis and COPD were significantly higher than those of healthy control group (P < 0.01 respectively). (2) The levels of ET in the culture supernatants of AMs and induced sputum were higher in heathy than those in patients with chronic bronchitis and COPD (P < 0.01 respectively). But there were no differences between patients with chronic bronchitis and COPD (P > 0.05 respectively). (3) Positive correlation was found between the levels of ET in the culture supernatants of AMs and those in induced sputum (r = 0.741, P < 0.01), between the number of AMs and the levels of ET in induced sputum (r = 0.597, P < 0.01). (4) Negative correlation was found between FEV(1)% of predicted value and the levels of ET in the culture supernatants of AMs in patients with COPD (r = -0.828, P < 0.01), between FEV(1)% of predited value and the levels of ET in induced sputum in patients with COPD (r = -0.748, P < 0.05). (5) In the culture with aminophylline, the level of ET derived from AMs remained stable (P > 0.05). But in the culture with LPS, the level of ET was significantly higher than that in the culture with DMEM (P < 0.01). CONCLUSIONS: (1) The characteristics of non-specific airway inflammation in patients with chronic bronchitis and COPD is the increased numbers of neutrophils and AMs. (2) AMs are perhaps important sources of ET in the lung. LPS can stimulate AMs to secrete more ET. ET derived from AMs takes part in development of COPD.