Kowalski M L, Didier A, Lundgren J D, Igarashi Y, Kaliner M A
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Respirology. 1997 Dec;2(4):267-74. doi: 10.1111/j.1440-1843.1997.tb00088.x.
Neurogenic inflammation in the airways involves both mucosal oedema and plasma protein exudation into the airway lumen. We aimed to investigate the mechanism of exudation of plasma proteins into the airway lumen. Neurogenic inflammation was induced in anaesthetized Sprague-Dawley rats by electrical stimulation of both vagal nerves at 20 V, 10 Hz, 5 ms. Vascular permeability was measured as 125I-albumin extravasation into both the airway wall and tracheobronchial lavage fluid. Following vagal stimulation, tracheobronchial lavages were analysed for albumin, total protein, histamine, immunoreactive substance P (SP), and immunoreactive calcitonin gene-related peptide (CGRP). Vagal stimulation rapidly increased vascular permeability in the airway mucosa and induced exudation of plasma proteins into the tracheobronchial fluid. Pre-treatment with capsaicin inhibited both neurogenic vascular permeability and movement of albumin into the airway lumen. SP and CGRP were detectable in basal lavages (1.37+/-0.12 ng/mL and 2.17+/-0.21 ng/mL, respectively) and the concentration of SP fell by 43% following treatment with capsaicin. Following vagal stimulation, concentrations of both SP and CGRP decreased significantly. Although basal tracheobronchial lavages contained histamine, vagal stimulation did not increase the histamine concentration. These results indicate that both neurogenic vascular permeability and plasma protein exudation into the airway lumen results from activation of capsaicin-sensitive sensory nerves and the reaction is not associated with mast cell activation.
气道中的神经源性炎症涉及黏膜水肿和血浆蛋白渗出到气道腔中。我们旨在研究血浆蛋白渗出到气道腔中的机制。通过以20V、10Hz、5ms的强度电刺激麻醉的Sprague-Dawley大鼠的双侧迷走神经来诱导神经源性炎症。通过测量125I-白蛋白渗入气道壁和气管支气管灌洗液来测定血管通透性。迷走神经刺激后,对气管支气管灌洗液进行白蛋白、总蛋白、组胺、免疫反应性P物质(SP)和免疫反应性降钙素基因相关肽(CGRP)的分析。迷走神经刺激迅速增加气道黏膜的血管通透性,并诱导血浆蛋白渗出到气管支气管液中。用辣椒素预处理可抑制神经源性血管通透性和白蛋白向气道腔的移动。在基础灌洗液中可检测到SP和CGRP(分别为1.37±0.12ng/mL和2.17±0.21ng/mL),用辣椒素处理后SP浓度下降了43%。迷走神经刺激后,SP和CGRP的浓度均显著降低。尽管基础气管支气管灌洗液中含有组胺,但迷走神经刺激并未增加组胺浓度。这些结果表明,神经源性血管通透性和血浆蛋白渗出到气道腔中均是由辣椒素敏感的感觉神经激活所致,且该反应与肥大细胞激活无关。