神经生长因子在哮喘患者诱导痰炎性细胞的表达

The expression of nerve growth factor in inflammatory cells of induced sputum from patients with asthma

目的 通过观察神经生长因子 (NGF)在哮喘气道炎性细胞的表达 ,探讨NGF与哮喘气道炎症形成的关系。方法 取 11例哮喘急性发作期、19例哮喘非急性发作期患者及 11例健康对照者的诱导痰 ,其中 12例哮喘非急性发作期患者予丙酸氟替卡松 (ICS)治疗 2周后再取诱导痰。做诱导痰炎性细胞分类计数 ;SP法测诱导痰炎性细胞NGF表达 ;ELISA测其上清中白细胞介素 (IL) 5浓度。结果 (1)诱导痰巨噬细胞、淋巴细胞、粒细胞NGF表达阳性率哮喘组较健康对照组高 (P值均<0 0 1) ,且急性发作期较非急性发作期高 (P <0 0 1)。急性发作期IL 5水平较非急性发作期和健康对照组高 (P值均 <0 0 1)。 (2 ) 12例非急性发作期患者经ICS治疗后 ,诱导痰巨噬细胞、淋巴细胞、粒细胞NGF表达阳性率及IL 5水平均较治疗前下降 (P值均 <0 0 1)。 (3)巨噬细胞、粒细胞NGF表达阳性率与淋巴细胞相对计数构成比、IL 5水平均呈正相关。结论 哮喘患者气道内巨噬细胞、淋巴细胞和粒细胞NGF表达增加 ,提示NGF可能与哮喘气道炎症的形成有关。

Objective To investigate the expression of nerve growth factor (NGF) in inflammatory cells of induced sputum from patients with asthma. Methods Induced sputum samples were collected from 11 asthmatics in exacerbation, 19 asthmatics with stable disease and 11 healthy individuals. Sputum samples of 12 asthmatics with stable disease were collected again after treatment with inhaled corticosteroids (ICS) for 2 weeks. The differential counts of sputum inflammatory cells were studied. NGF was detected using immunocytochemistry and the positive percentages in different cells were measured. Interleukin-5 (IL-5) in sputum supernatants was detected using enzyme-linked immunosorbent assay.Results NGF was localized in the plasma of macrophages, lymphocytes and granulocytes. (1) In asthmatics with both exacerbation and stable disease, the NGF positive percentages in macrophages[(77.8±4.8)% and (68.1± 5.3)%], lymphocytes [(43.2±9.3)% and (34.2±11.3)%], and granulocytes[(38.7±6.2)% and (32.1±3.7)%] were all significantly higher (P<0.01) than those in the healthy controls [(37.6±8.4)%, (12.6±8.5)%,and (12.7±8.2)%, respectively]. The differences of those indices between patients with exacerbation and patients with stable disease were also significant (P<0.01). Patients with exacerbation had significantly elevated levels of IL-5 [(124±71)ng/L] compared with patients with stable disease [(52±23) ng/L] and the healthy controls[(26±12) ng/L] (P<0.01). (2) In the 12 patients with stable disease evaluated after treatment with ICS, the NGF positive percentages in macrophages [(54.3±7.3)%], lymphocytes[(22.0±5.6)%], and granulocytes[(27.0±4.3)%], and the level of IL-5[(29±13) ng/L] were all decreased significantly(P<0.01) compared with the baselines [(67.0±5.0)%, (36.0± 9.0)%, (32.0±3.0)%, and (49±26) ng/L, respectively]. (3) The NGF positive percentages in both macrophages and granulocytes correlated to the sputum lymphocyte counts (r=0.723, r=0.630, P<0.01; respectively) and the levels of IL-5(r=0.652, r=0.636, P<0.01;respectively). Conclusion The expression of NGF in macrophages and lymphocytes in the airways is upregulated in asthma, which indicates a potential correlation between NGF and airway inflammation in asthma.