Oldenburg Peter J, Mustafa S Jamal
Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
J Pharmacol Exp Ther. 2005 Apr;313(1):319-24. doi: 10.1124/jpet.104.071720. Epub 2004 Dec 30.
In allergen-induced asthma, activation of lung mast cells leads to bronchial constriction, increased mucus secretion, and an increase in the localization of inflammatory cells to the airways. The purpose of this study was to explore the role of mast cells in adenosine-mediated airway reactivity and inflammation using the mast cell degranulating agent, compound 48/80 (C48/80). Mice were sensitized and challenged with ragweed (or 0.9% saline) followed by C48/80 administration twice a day in increasing doses for 5 days. Dose-responsiveness to the nonspecific adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) was established, and lung lavage was performed 24 h later for cell differential analysis to evaluate inflammation. At a dose of 375 microg/ml (aerosolized NECA), C48/80 pretreatment resulted in a significant attenuation in airway reactivity when compared with sensitized control mice (330.07 versus 581.57%, respectively). Lung lavage from the C48/80 treated mice showed a decrease in eosinophils (17.7 versus 60.9%, respectively) and an increase in macrophages when compared with the sensitized control group (76.4 versus 30.8%, respectively). These results support the conclusion that mast cell degranulation plays an important role in adenosine receptor-mediated airway hyperresponsiveness and inflammation.
在变应原诱导的哮喘中，肺肥大细胞的激活会导致支气管收缩、黏液分泌增加以及炎症细胞在气道中的定位增加。本研究的目的是使用肥大细胞脱颗粒剂化合物48/80（C48/80）来探讨肥大细胞在腺苷介导的气道反应性和炎症中的作用。小鼠用豚草（或0.9%盐水）致敏并激发，随后每天两次给予递增剂量的C48/80，持续5天。建立对非特异性腺苷受体激动剂5'-N-乙基羧酰胺腺苷（NECA）的剂量反应性，并在24小时后进行肺灌洗以进行细胞分类分析来评估炎症。在剂量为375微克/毫升（雾化NECA）时，与致敏对照小鼠相比，C48/80预处理导致气道反应性显著减弱（分别为330.07%对581.57%）。与致敏对照组相比，C48/80处理小鼠的肺灌洗显示嗜酸性粒细胞减少（分别为17.7%对60.9%），巨噬细胞增加（分别为76.4%对30.8%）。这些结果支持肥大细胞脱颗粒在腺苷受体介导的气道高反应性和炎症中起重要作用这一结论。
