Olgart Höglund C, de Blay F, Oster J P, Duvernelle C, Kassel O, Pauli G, Frossard N
Eur Respir J. 2002 Nov;20(5):1110-6. doi: 10.1183/09031936.02.00205402.
Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa. BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections. The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects. This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo, and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from the increase in nerve growth factor-immunopositive cells determined in the bronchial submucosa.
最近有研究表明神经生长因子（NGF）是炎症的重要介质。与此观点相符的是，哮喘患者血清中的NGF水平已被证实有所升高。然而，与健康受试者相比，哮喘气道局部的NGF水平是否也会发生改变尚未得到证实，而且人类支气管中NGF潜在来源的定位也尚未被描述。本研究的目的是评估哮喘患者支气管肺泡灌洗液（BALF）中的NGF水平，并与对照组受试者进行比较。此外，作者还想确定支气管组织中NGF的潜在来源，并对支气管黏膜下层中NGF免疫阳性浸润细胞进行计数。通过纤维支气管镜从7名对照受试者和7名哮喘患者中获取BALF和支气管活检样本。采用酶联免疫吸附测定法对BALF中的NGF蛋白水平进行定量。通过免疫组织化学方法在支气管活检切片上检测NGF的定位。哮喘患者BALF中的NGF水平显著升高。在支气管上皮、平滑肌细胞和黏膜下层浸润的炎症细胞中观察到强烈的NGF免疫反应性，在结缔组织中反应较弱。哮喘患者支气管黏膜下层中NGF免疫反应性浸润细胞的数量高于对照受试者。本研究提供了证据表明神经生长因子在气道中是局部产生的，并且表明在哮喘患者中这种产生会增强。这些发现表明神经生长因子是由体内人类支气管中的结构细胞和浸润的炎症细胞产生的，作者认为哮喘患者支气管肺泡灌洗液中观察到的神经生长因子蛋白增加可能既源于结构细胞在炎症状态下产生的神经生长因子水平升高，也源于支气管黏膜下层中神经生长因子免疫阳性细胞的增加。
