Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation
Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation
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DOI：
10.1165/ajrcmb.21.4.3670
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发表时间：
1999-10-01
影响因子：
6.4
通讯作者：
Renz, H
中科院分区：
文献类型：
--
作者：
Braun, A;Lommatzsch, M;Renz, H
本研究的目的是探讨过敏性哮喘患者脑源性神经营养因子(BDNF)的产生及其细胞来源。为此，我们建立了一种慢性重度卵蛋白(OVA)诱导的小鼠呼吸道炎症模型。接触过敏原的小鼠出现免疫球蛋白E效价升高；淋巴细胞、单核细胞和嗜酸性粒细胞涌入引起的呼吸道炎症；以及呼吸道高反应性。除炎症细胞外，白介素4和白介素5的产生增加，巨噬细胞出现激活的形态迹象，呼吸道上皮增厚，呈杯状细胞增生，粘液产生明显。采用原位杂交和酶联免疫吸附试验检测脑源性神经营养因子的表达。致敏和非致敏小鼠肺上皮细胞中均有BDNF信使RNA的结构性表达。此外，在OVA致敏和气雾剂激发的小鼠的气道炎性浸润物和支气管肺泡灌洗液(BALF)细胞中也检测到BDNF mRNA。长期接触变应原气雾剂后，BALF中BDNF蛋白水平最高。对分离的淋巴细胞亚群产生BDNF的分析表明，T细胞而不是B细胞是BDNF的细胞来源。此外，活化的肺泡巨噬细胞被鉴定为BDNF阳性细胞。这些数据表明，在过敏性呼吸道炎症中，BDNF的产生被上调，免疫细胞是BDNF的来源。
The aim of this study was to investigate production and cellular sources of brain-derived neurotrophic factor (BDNF) production in allergic asthma. For this purpose a mouse model of chronic and severe ovalbumin (OVA)-induced airway inflammation was developed. Allergen-exposed mice developed elevated immunoglobulin E titers; airway inflammation with influx of lymphocytes, monocytes, and eosinophils; and airway hyperresponsiveness. In addition to an influx of inflammatory cells, interleukin (IL)-4 and IL-5 production were enhanced, macrophages showed morphologic signs of activation, and airway epithelium was thickened and displayed a goblet-cell hyperplasia with a marked mucus production. BDNF was detected using in situ hybridization and enzyme-linked immunosorbent assay. Constitutive expression of BDNF messenger RNA (mRNA) was observed in the respiratory epithelium of sensitized and nonsensitized mouse lungs. In addition, BDNF mRNA was detected in airway inflammatory infiltrations and bronchoalveolar lavage fluid (BALF) cells of OVA-sensitized and aerosol-challenged mice. Highest BDNF protein levels were detected in BALF after long-term allergen aerosol exposure. Analysis of BDNF production by isolated lymphocyte subsets revealed T but not B cells as a cellular source of BDNF. In addition, activated alveolar macrophages were identified as BDNF-positive cells. These data indicate that in allergic airway inflammation BDNF production is upregulated and immune cells serve as a source of BDNF.