Nassenstein Christina, Braun Armin, Erpenbeck Veit Johannes, Lommatzsch Marek, Schmidt Stephanie, Krug Norbert, Luttmann Werner, Renz Harald, Virchow Johann Christian
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
J Exp Med. 2003 Aug 4;198(3):455-67. doi: 10.1084/jem.20010897.
Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of neurotrophins on eosinophil function in allergic asthma. Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.
在过敏性疾病中已观察到神经营养因子(神经生长因子[NGF]、脑源性神经营养因子[BDNF]、神经营养蛋白[NT]-3和NT-4)浓度升高。变应原激发后,支气管内神经营养因子水平上调。这与活化的嗜酸性粒细胞流入支气管腔同时发生。这些嗜酸性粒细胞在节段性变应原激发(SAP)后18小时活力增加且CD69表达上调,而外周血中不存在这种情况。为了研究这些观察结果是否相关,我们研究了神经营养因子对过敏性哮喘中嗜酸性粒细胞功能的影响。用NGF、BDNF、NT-3或NT-4孵育可导致支气管肺泡灌洗液(BALF)中分离的嗜酸性粒细胞活力和CD69表达显著增加,但外周血中的嗜酸性粒细胞则无此现象,这表明支气管内嗜酸性粒细胞对神经营养因子具有独特的敏感性。为了阐明潜在机制,通过RT-PCR和免疫细胞学法分析了嗜酸性粒细胞上神经营养因子受体p75NTR、trkA、trkB和trkC的表达。SAP后,BALF中嗜酸性粒细胞上所有神经营养因子受体的表达均显著升高。我们的研究结果表明,神经营养因子介导的支气管嗜酸性粒细胞活化可能在过敏性哮喘嗜酸性粒细胞炎症的调节中起作用。