Segmental antigen challenge increases fibronectin in bronchoalveolar lavage fluid
Segmental antigen challenge increases fibronectin in bronchoalveolar lavage fluid
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DOI：
10.1164/ajrccm.159.2.9806053
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发表时间：
1999-02-01
影响因子：
24.7
通讯作者：
Jarjour, NN
中科院分区：
文献类型：
--
作者：
Meerschaert, J;Kelly, EAB;Jarjour, NN
纤维连接蛋白可能通过募集和激活炎症细胞，促进上皮下纤维化，从而参与哮喘的发病。纤维连接蛋白由几种类型的呼吸道细胞产生，包括上皮细胞、成纤维细胞和肺泡巨噬细胞。为了验证抗原诱导的呼吸道炎症与局部纤维连接蛋白生成增加有关的假设，对17例特应性患者进行了抗原和生理盐水节段性支气管激发(SBP)。分别于生理盐水或抗原刺激后5min和48h行支气管肺泡灌洗(BAL)。用酶联免疫吸附试验(EL ISA)检测，BAL液中纤维连接蛋白浓度在抗原攻击后48小时增加了5倍以上(中位数为65[47~110]ng/ml，中位数为407[240~697]ng/ml，四分位数间距为25~75%，p<；0.05)。抗原攻击后48h的纤维连接蛋白浓度与抗原攻击后5min的组胺浓度以及抗原攻击后48h BAL液中嗜酸性粒细胞、中性粒细胞、巨噬细胞和总细胞数呈正相关。与单纯从血浆蛋白通透性增加预测的结果相比，BAL在攻击后48小时内纤维连接蛋白的含量更高。Western印迹分析显示，BAL液中的纤维连接蛋白基本完整，并含有细胞纤维连接蛋白的额外A结构域(ED-A)剪接变异体，表明局部产生。我们的结论是，特应性受试者的抗原攻击导致气道细胞产生纤维连接蛋白的增加，并推测这种反应可能有助于过敏性炎症中的气道重塑。
Fibronectin may contribute to asthma pathogenesis by recruitment and activation of inflammatory cells, and by promotion of subepithelial fibrosis. Fibronectin is produced by several types of airway cells, including epithelial cells, fibroblasts, and alveolar macrophages. To test the hypothesis that antigen-induced airway inflammation is associated with increased local generation of fibronectin, segmental bronchoprovocation (SBP) with antigen and saline was performed in 17 atopic patients. Bronchoalveolar lavage (BAL) was performed at 5 min and 48 h after segmental challenge with saline or antigen. Fibronectin concentrations in BAL fluid, measured by enzyme-linked immunosorbent assay (ELISA), increased more than 5-fold 48 h after antigen challenge (65 [47 to 110] versus 407 [240 to 697] ng/ml, median and 25 to 75% interquartiles, p < 0.05). Fibronectin concentrations 48 h after antigen challenge correlated with histamine concentrations 5 min after antigen challenge and numbers of eosinophils, neutrophils, macrophages, and total cells in BAL fluid 48 h after antigen challenge. BAL was more enriched in fibronectin 48 h after challenge than would be predicted solely from increased permeability of plasma proteins. Western blot analysis showed that fibronectin in BAL fluid was largely intact and contained the extra domain-A (ED-A) splice variant of cellular fibronectin, indicative of local production. We conclude that antigen challenge in atopic subjects causes increased production of fibronectin by airway cells and speculate that this response may contribute to airway remodeling in allergic inflammation.